BACKGROUND: The potential impacts of polygenic scores (PGS) on health-behavior changes are not fully understood. The Iwate PGS Assessment and Risk Communication Study aims to investigate the effects of reporting PGS-based risk for ischemic stroke on health behaviors. METHODS: Participants wishing to know their PGS-based ischemic stroke risk were recruited from health checkup venues for workers in Iwate Prefecture in 2023. Health checkup data, biospecimens, and questionnaire responses were collected for biochemical testing, genotyping, and storage in the Tohoku Medical Megabank integrated biobank. The risk was calculated using an integrative PGS model for East Asians. Participants were randomly assigned to two groups, and one group received their risk report as the intervention group. The impacts of the risk notification will be investigated in follow-up surveys. RESULTS: Of 3,599 workers, 2,088 participated in the study (consent rate: 58.0%). The demographic profile of the eligible 2,083 participants was as follows: 80.7% males, and dominance of participants aged 18-29 years (25.2%), in their 30's (25.3%), and in their 40's (24.7%). Two hundred participants (9.7%) had a risk of 1.0 as the reference; 57 (2.7%), 927 (44.7%), and 888 (42.9%) participants had 2.1-3.4-, 1.4-1.9-, and <1.0-fold that risk, respectively. CONCLUSION: We collected health information and biospecimens from over 2,000 workers and disclosed the PGS-based ischemic stroke risk. Behavioral effects will be evaluated 1 year after disclosure, with follow-up until 2030. As Japan's first large-scale PGS risk communication study, it will provide initial insights for implementing PGS in personalized preventive medicine.

Antihypertensive therapy has reduced cardiovascular mortality; however, challenges remain, including residual risk in treated patients and the population burden associated with borderline hypertension. Previous Japanese estimates of the population attributable fraction (PAF) are derived from older cohorts and often lacked stratification by treatment status. We conducted a prospective study of 61,495 participants (women: 56.7%, aged 60.7 ± 11.0 years) from the Tohoku Medical Megabank Community-Based Cohort Study. Participants were classified into six blood pressure (BP) categories based on the JSH 2019 guidelines, and further stratified by hypertension treatment status, resulting in 12 groups. Using untreated individuals with normal BP as the reference, we calculated multivariable-adjusted hazard ratios (HR), 95% confidence intervals (CI), and PAF for the remaining groups using Cox proportional hazards model. During a median follow-up of 6.5 years, 1909 deaths were recorded. HRs increased with rising BP in both untreated and treated participants. The overall PAF for all-cause mortality due to non-normal BP was 9.45%, with a marked sex difference (12.25% in male and 5.16% in female). The highest PAF contributions were observed in the treated Grade I hypertension group (2.18%) and the untreated elevated BP group (1.28%). In this contemporary Japanese cohort, non-normal BP accounts for 9.45% of all-cause mortality, representing a substantial public health burden, particularly among men. The substantial PAF contributions from both treated patients and untreated individuals with elevated BP highlight the importance of effective BP management for both primary and secondary prevention.

BACKGROUND: Preserved ratio impaired spirometry (PRISm), defined as a forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) ratio ≥0.70 and a predicted FEV1 <80 %, is associated with increased morbidity and mortality. However, determinants of PRISm, particularly in younger populations, remain poorly characterised. We aimed to address this knowledge gap. METHODS: We conducted a cross-sectional analysis of 12,350 participants from a Japanese community-based cohort using data from the Tohoku Medical Megabank Project. Participants underwent spirometry, blood pressure measurement, laboratory testing, and completed standardised questionnaires. Multivariate logistic regression was used to identify factors associated with PRISm across three age groups: 20-39, 40-59, and ≥60 years. Interactions between age groups and other explanatory variables were assessed. RESULTS: In the 20-39-year group, PRISm was independently associated with being men, diabetes mellitus, hypothyroidism, and low body mass index (BMI <18.5 kg/m2), and inversely associated with age. Among participants aged ≥60 years, PRISm was significantly associated with increasing age, overweight status (BMI ≥25.0-<30.0 kg/m2), being men, current smoking, hypertension, diabetes mellitus, bronchial asthma, elevated eosinophil counts (≥300 cells/μL), and birth weight ≥2000-<2500 g. Significant interactions were observed between age and BMI, bronchial asthma, and thyroid dysfunction. CONCLUSIONS: Our findings indicate that PRISm in younger adults is associated with hypothyroidism and underweight status, whereas in older adults, it is more closely related to constitutional and lifestyle-related factors. These results highlight the heterogeneity of PRISm and indicate that its pathophysiology and optimal management may vary by age group.

Family history of hypertension may reflect genetic and lifestyle factors. Genetic risk can be assessed using polygenic risk score (PRS); however, whether PRS can stratify hypertension risk when combined with family history and lifestyle information is unclear. This prospective cohort study included 9,001 hypertension-free individuals aged ≥20 years from the Tohoku Medical Megabank Community-Based Cohort Study. Participants were scored on lifestyle factors, including body mass index, urinary sodium-to-potassium ratio, physical activity, alcohol consumption, and smoking at recruitment. During the mean follow-up of 4.3 years, 2822 (31.4%) cases of hypertension occurred. High genetic risk and poor lifestyle were associated with increased hypertension risk. Compared with participants with low genetic risk, ideal lifestyle, and no family history, high genetic risk significantly increased hypertension risk, even among those with ideal lifestyle and no family history (relative risk [RR] 1.28 [95% confidence interval [CI] 1.11-1.46]). Participants with low PRS, ideal lifestyle, but with family history had increased hypertension risk (RR 1.32 [95%CI 1.11-1.57]). Poor lifestyle increased hypertension risk across most genetic risk groups, regardless of family history. Integrating PRS into models with family history and lifestyle risk significantly improved predictive accuracy (area under the curve: 0.671 for family history and lifestyle risk and 0.674 for PRS integrated; P for difference <0.05). Integrating PRS with lifestyle and family history enhances the stratification of individuals at high risk for hypertension.

BACKGROUND: Whether adherence to a healthy lifestyle can mitigate genetic risk for renal dysfunction remains unclear. METHODS: This prospective cohort study included 12 680 adults aged ≥20 years, free from chronic kidney disease at baseline, enrolled in the Tohoku Medical Megabank Community-based Cohort study. A healthy lifestyle score-based on normal weight, never smoking, never drinking, regular physical activity, and a low urinary sodium-to-potassium ratio-classified participants into ideal, intermediate, or poor lifestyle groups. A polygenic risk score (PRS) was constructed using estimated glomerular filtration rate (eGFR) data from a previous multi-ancestry genome-wide association meta-analysis. The primary outcome was renal dysfunction, defined as eGFR <60.0 ml/min/1.73 m2. RESULTS: Among the 12 680 adults, 123 participants (0.9%) developed renal dysfunction during a mean follow-up of 4.4 ± 0.8 years. Poor lifestyle was consistently associated with higher risk of renal dysfunction across most PRS categories. Participants with intermediate genetic risk had elevated risk only when also exhibiting an intermediate lifestyle. Formal testing for effect modification by PRS provided modest evidence that the association between high genetic risk and increased risk of renal dysfunction was stronger among individuals with an intermediate lifestyle. Although the addition of the PRS to the model included the C-statistic, this improvement was not statistically significant. CONCLUSIONS: Maintaining a healthy lifestyle is associated with lower risk of renal dysfunction, regardless of genetic risk. Combining PRSs with lifestyle information may enhance risk stratification, although further studies are needed to improve predictive accuracy.

PURPOSE: This study was conducted to elucidate the distribution and determinants of ocular biometric parameters and to assess the association between intraocular pressure (IOP) and single nucleotide polymorphisms (SNPs) in the Japanese population-based genome cohort studies. DESIGN: Cross-sectional analysis involving genome-wide association studies (GWASs). PARTICIPANTS: In total, 22 150 participants aged >18 years from the population cohort (Community-Based Cohort [CommCohort]) and 11 302 participants from the Birth and Three-Generation (BirThree) Cohort of the Tohoku Medical Megabank Organization Eye Study were examined. METHODS: Participant underwent interviews, ophthalmic and physiological examinations, laboratory tests, and microarray analyses. Genome-wide association studies were conducted in the CommCohort (discovery stage) and the BirThree Cohort (replication stage), followed by a meta-analysis. Associations of SNPs and IOP were evaluated using a genome-wide significance threshold (5 × 10- 8). MAIN OUTCOME MEASURES: Association of SNPs with IOP and distributions of IOP by sex and age. RESULTS: In the discovery stage, the mean IOP of the right and left eye was 13.95 and 14.02 mmHg, respectively. In the replication stage, the corresponding values were 14.32 and 14.27 mmHg, respectively. A significant age-related reduction in IOP was observed in both stages (P < 0.001). Genome-wide association studies identified 573 and 2 genome-wide significant SNPs in the discovery and replication stages, respectively. Meta-analysis revealed 1601 significant SNPs across 21 loci on 11 chromosomes (Chrs). Of these loci, 17 were previously known to be associated with IOP or glaucoma, while four-septin-8 (SEPT8; Chr5), aldehyde dehydrogenase 2 (ALDH2; Chr12), collagen type VI alpha 2 chain (COL6A2; Chr21), and Wnt family member 7B (WNT7B; Chr22)-were newly identified. CONCLUSIONS: This large-scale GWAS in a Japanese population identified 21 loci associated with IOP, including 4 novel loci. The findings highlight both genetic similarities and population-specific variations in SNPs influencing IOP and provide valuable insights to enhance eye health care, including glaucoma management. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

BACKGROUND: No previous studies have explored metabolites associated with both genetic predispositions to type 2 diabetes (T2DM) and T2DM onset. Therefore, we aimed to explore metabolic profiles using genetic risk to identify pathways for tailored T2DM prevention strategies. METHODS: This prospective community-based cohort study in Japan included a total of 12,461 participants aged ≥ 20 years. Genetic predictors were genome-wide and pathway-based polygenic risk scores (PRSs). We quantified 43 metabolites using nuclear magnetic resonance spectroscopy. T2DM was defined as a non-fasting glucose level of ≥ 200 mg/dL, glycated hemoglobin level ≥ 6.5%, or self-reported T2DM treatment. A modified Poisson regression model was used to examine the associations of PRSs and metabolites with T2DM incidence. Linear associations were tested using the restricted cubic spline, and mediation analysis was conducted to assess the mediating effect of metabolites on the association between PRSs and T2DM incidence. RESULTS: During the 4.3-year median follow-up period, 354 T2DM cases were identified. A higher PRS was associated with incident T2DM (relative risk [RR] 2.09, 95% confidence interval [CI], 1.68-2.60, P < 0.001, 1-standard deviation [SD] increment). The nitrogen compound transport pathway PRS was associated with incident T2DM (RR 1.32, 95% CI 1.03-1.70, P < 0.001, 1-SD increment). Fourteen metabolites like glucose, 2-ketoisocaproic acid, glutamic acid, leucine, 2-aminobutyric acid, 2-hydroxybutyric acid, valine, 3-methyl-2-oxobutyric acid, alanine, 3-hydroxybutyric acid, 3-methyl-2-oxiovaleric acid, formic acid, arginine, and tyrosine were positively associated with the risk of T2DM. Only glycine was inversely associated with the risk of T2DM. Among 43 metabolites, 14 metabolites were positively associated with PRS (P for linear trend < 0.05). 3-hydroxyisobutyric-acid, 2-Aminobutyric acid, 2-ketoisocaproic acid, 2-hydroxybutyric acid, leucine, glycine, and glucose mediated the association between PRS and incident T2DM. CONCLUSIONS: Several metabolites were found to mediate the association between PRS and incident T2DM. These findings may contribute to a better understanding of the metabolic pathways involved in genetic susceptibility to T2DM.

Preterm birth is one of the most important neonatal complications. In this study, we aimed to establish an artificial intelligence model for early prediction of preterm birth. Based on genetic and lifestyle data from over 20,000 neonates, we developed high-performed early prediction models up to 0.92 of AUC. Our developed models will help early prediction and appropriate intervention of preterm birth.

Personalized prevention based on individual health data is vital in modern healthcare. We analyzed four years of checkup data from 96,093 individuals (20-74 years) to map transitions from healthy states to mibyo (pre-disease) and disease onset. Using dimensionality reduction and clustering, we identified 43 male and 33 female health status clusters, revealing distinct transition trajectories that inform targeted preventive strategies.

INTRODUCTION: While social capital can prevent diabetes, these benefits can be heterogeneous with respect to socioeconomic status. We investigated the association between social capital and gestational diabetes mellitus (GDM) while examining effect modification by household income. MATERIALS AND METHODS: We conducted a secondary data analysis using the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study carried out between July 2013 and March 2017. Social capital (mutual aid, social trust, informal social control, collective action) and covariates were self-reported, while GDM diagnosis and other medical and physiological information were obtained from medical records. To assess the association between social capital and GDM, we conducted logistic regression models. We further tested for interactions between social capital and household income as well as stratified the models by income. RESULTS: Among 20,339 study participants, 700 (3.4%) were diagnosed with GDM. Multivariable logistic regression models found that social trust and collective action were associated with lower GDM prevalence, even after adjustment of covariates. When stratifying household income, however, social capital was significantly associated with the reduced risks of GDM only among participants with higher household income (OR: 0.90, 95% CI: 0.85-0.97). No significant association was observed among those with lower household income. CONCLUSIONS: The health benefit of social capital on GDM prevalence was heterogeneous, and the protective effect of social capital on GDM was found only among women with higher household income. The differential impact of social capital on GDM highlights the need for targeted interventions addressing structural health inequities.

BACKGROUND: Dry eye disease (DED) is a common ocular condition with diverse and heterogeneous symptoms. Current treatment standards of DED include the post facto management of associated symptoms through topical eye drops. However, there is a need for predictive, preventive, personalized, and participatory medicine. The DryEyeRhythm mobile health app enables real-time data collection on environmental, lifestyle, host, and digital factors in a patient's daily environment. Combining these data with genetic information from biobanks could enhance our understanding of individual variations and facilitate the development of personalized treatment strategies for DED. OBJECTIVE: This study aims to integrate digital data from the DryEyeRhythm smartphone app with the Tohoku Medical Megabank database to create a comprehensive database that elucidates the interplay between multifactorial factors and the onset and progression of DED. METHODS: This prospective observational cohort study will include 1200 participants for the discovery stage and 1000 participants for the replication stage, all of whom have data available in the Tohoku Medical Megabank database. Participants will be recruited from the Community Support Center of Sendai, Miyagi Prefecture, Japan. Participant enrollment for the discovery stage was conducted from August 1, 2021, to June 30, 2022, and the replication stage will be conducted from August 31, 2024, to March 31, 2026. Participants will provide demographic data, medical history, lifestyle information, DED symptoms, and maximum blink interval measurements at baseline and after 30 days using the DryEyeRhythm smartphone app. Upon scanning a registration code, each participant's cohort ID from the Tohoku Medical Megabank database will be linked to their smartphone app, enabling data integration between the Tohoku Medical Megabank and DryEyeRhythm database. The primary outcome will assess the association between genetic polymorphisms and DED using a genome-wide association study. Secondary outcomes will explore associations between DED and various factors, including sociodemographic characteristics, lifestyle habits, medical history, biospecimen analyses (eg, blood and urine), and physiological measurements (eg, height, weight, and eye examination results). Associations will be evaluated using logistic regression analysis, adjusting for potential confounding factors. RESULTS: The discovery stage of participant enrollment was conducted from August 1, 2021, to June 30, 2022. The replication stage will take place from August 31, 2024, to March 31, 2026. Data analysis is expected to be completed by September 2026, with results reported by March 2027. CONCLUSIONS: This study highlights the potential of smartphone apps in advancing biobank research and deepening the understanding of multifactorial DED, paving the way for personalized treatment strategies in the future. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/67862.

Gestational diabetes mellitus (GDM) is common in Japanese women, posing serious risks to mothers and offspring. This study investigated the influence of maternal genotypes on the risk of GDM and examined how these genotypes modify the effects of psychological and dietary factors during pregnancy. We analyzed data from 20,399 women in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort. Utilizing two customized SNP arrays for the Japanese population (Affymetrix Axiom Japonica Array v2 and NEO), we performed a meta-analysis to combine the datasets. Gene-environment interactions were assessed by modeling interaction terms between genome-wide significant single nucleotide polymorphisms (SNPs) and psychological and dietary factors. Our analysis identified two SNP variants, rs7643571 (p = 9.14 × 10-9) and rs140353742 (p = 1.24 × 10-8), located in an intron of the MDFIC2 gene, as being associated with an increased risk of GDM. Additionally, although there were suggestive patterns for interactions between these SNPs and both dietary factors (e.g., carbohydrate and fruit intake) and psychological distress, none of the interaction terms remained significant after Bonferroni correction (p < 0.05/8). While nominal significance was observed in some models (e.g., psychological distress, p = 0.04), the data did not provide robust evidence of effect modification on GDM risk once adjusted for multiple comparisons. These findings reveal novel genetic associations with GDM in Japanese women and highlight the importance of gene-environment interactions in its etiology. Given that previous genome-wide association studies (GWAS) on GDM have primarily focused on Western populations, our study provides new insights by examining an Asian population using a population-specific array.

BACKGROUND: Early detection and management of atrial fibrillation (AF) are crucial. Combined models incorporating genetic risks and clinical risks have been developed to improve predictive ability. Although sex differences have been reported in many aspects of AF, sex differences in genetic risk have not been studied. OBJECTIVE: The purpose of this study was to assess the sex difference in the effect of polygenic risk score for AF (AF-PRS) on AF prevalence using cross-sectional data from the Tohoku Medical Megabank Project Community-Based Cohort Study in Japan. METHODS: AF-PRS and Cohorts for Heart and Aging Research in Genomic Epidemiology Atrial Fibrillation (CHARGE-AF) score were used for genetic AF risks and clinical AF risks, respectively. Sex differences in the association of AF-PRS with the prevalence of AF were evaluated. RESULTS: Among 16,853 participants (mean age 63.4 years; 5182, 30.7% men), the prevalence of AF was 255 (4.9%) in men and 130 (1.1%) in women. In the group with high AF-PRS and high CHARGE-AF score, the odds ratio for AF was highest in men and women (8.2 in men and 9.4 in women), compared with that in the group with low AF-PRS and low CHARGE-AF score. Integrating AF-PRS into the CHARGE-AF score significantly enhanced the area under the receiver operating characteristic curve for AF in men (from 0.639 to 0.749) but not in women (from 0.710 to 0.733). CONCLUSION: Our study is the first to show a sex difference in the association of AF-PRS and AF prevalence. AF-PRS is more closely associated with the prevalence of AF in men than in women.

BACKGROUND: Natural disasters may have negative health effects on survivors. However, long-term observations on this are lacking. Therefore, this study investigated the association between the degree of housing damage caused by the Great East Japan Earthquake (GEJE) and all-cause mortality using the data from the cohort study conducted by the Tohoku Medical Megabank (TMM) Project in disaster-stricken areas. METHODS: The community-based cohort study of the TMM Project which conducted a baseline survey from May 2013 to March 2016 collected data using questionnaires and blood and urine tests. The present large-scale prospective cohort study was a follow-up survey in which the degree of house damage and all-cause mortality were analysed using Cox proportional hazards regression, adjusting for sex, age and other potentially confounding variables. The degree of house damage was categorised into 'did not live in the disaster area', 'no damage', 'small-scale damage' and 'large-scale damage'. Among the 58 320 participants, 1763 deaths were confirmed during the follow-up which averaged 6.5 years. RESULTS: The multivariate analysis showed a hazard ratio (95% CI) of 0.96 (0.82 to 1.13) for those who did not live in the disaster area, 0.98 (0.87 to 1.10) for small-scale damage and 0.98 (0.85 to 1.14) for large-scale damage, compared with no damage, but no significant association with all-cause mortality was observed. CONCLUSION: The results of this large-scale prospective cohort study of GEJE survivors showed no significant relationship between the degree of house damage and all-cause mortality. Further long-term follow-up studies are needed to examine the long-term health effects of natural disasters on survivors.

BACKGROUND: The primary prevention of atrial fibrillation (AF), which increases mortality through complications including stroke and heart failure, is important. Excessive salt intake and low potassium intake are risk factors for cardiovascular disease; however, their association with AF remains inconclusive. This study investigated the association between sodium- and potassium-related urinary markers and AF prevalence. METHODS AND RESULTS: Data from the Tohoku Medical Megabank Project Community-based Cohort Study were used in this cross-sectional study. The urinary sodium-to-potassium (Na/K) ratio and estimated 24-h sodium and potassium excretion were calculated using spot urine samples and categorized into quartiles (Q1-Q4). The prevalence of AF was the primary outcome. Of the 26,506 participants (mean age 64.8 years; 33.2% males) included in this study, 630 (2.4%) had AF. Using Q1 as the reference group, the odds ratios for AF prevalence in Q4 were 1.35 (95% confidence interval [CI] 1.07-1.73) and 1.59 (95% CI 1.20-2.12) for 24-h estimated urinary Na/K ratio and estimated 24-h sodium excretion, respectively. Estimated 24-h potassium excretion was not associated with AF prevalence. CONCLUSIONS: AF prevalence was positively associated with the urinary Na/K ratio and estimated 24-h urinary sodium excretion, but not with estimated 24-h urinary potassium excretion. Although further prospective studies are warranted, the findings of this study suggest that salt intake may be a modifiable risk factor for AF.

OBJECTIVES: Previous studies have assessed the impact of active smoking on mortality using the population-attributable fraction (PAF). However, these studies have not included second-hand smoking (SHS), potentially underestimating smoking's impact. We compared the PAF from active smoking alone with the PAF, including SHS exposure. DESIGN: Prospective cohort study. SETTING: A community-based cohort study in Japan. PARTICIPANTS: 40 796 participants aged ≥20 years. MAIN OUTCOME MEASURES: SHS was defined as inhaling someone else's cigarette smoke at the workplace or home in the past year. We classified smoking status and SHS into ten categories: never-smoker without SHS, never-smoker with SHS, past smoker without SHS, past smoker with SHS, current smoker 1-9 cigarettes/day without SHS, current smoker 1-9 cigarettes/day with SHS, 10-19 cigarettes/day without SHS, 10-19 cigarettes/day with SHS, ≥20 cigarettes/day without SHS and ≥20 cigarettes/day with SHS. The main outcome was all-cause mortality. RESULTS: During the median follow-up period of 6.5 (5.7-7.5) years, 788 men and 328 women died. For men, compared with never-smokers without SHS, past smokers without SHS (HR, 1.39 [95% CI, 1.11 to 1.73]) and past smokers with SHS (HR, 1.48 (95% CI, 1.10 to 2.00)) were associated with all-cause mortality. For women, never-smokers with SHS had a significantly higher risk of all-cause mortality (HR, 1.36 (95% CI, 1.00 to 1.84)). Without considering SHS, 28.0% and 2.3% of all-cause mortality in men and women, respectively, were attributable to past and current smoking. Including SHS, PAF increased to 31.3% in men and 8.4% in women. CONCLUSIONS: We clarified that smoking's impact was underestimated by not accounting for SHS, especially in women. Information on SHS is crucial for understanding smoking's health impact. This study supports the importance of avoiding smoking and preventing SHS.

BACKGROUND: Studies investigating whether respiratory syncytial virus (RSV) infection, non-RSV respiratory infections, respiratory-related disorders, and non-respiratory-related disorders are associated with subsequent wheezing are limited in Japan. We aimed to elucidate the relationship between hospitalization for RSV infection, non-RSV respiratory infections, respiratory-related disorders, as well as non-respiratory-related disorders and subsequence wheezing in Japanese children. METHODS: This study included 7340 children and was conducted under the TMM BirThree Cohort Study (Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study). Data was collected from birth records and questionnaires. We categorized hospitalization history into five categories: "no hospitalization," hospitalizations for "RSV infection," "non-RSV respiratory infections," "respiratory-related disorders," and "non-respiratory-related disorders." The association of the five categories with later wheezing at 3 years of age was evaluated using multivariable logistic regression analysis. RESULTS: After adjusting for covariates, an association was shown between hospitalization under 2 years of age and later wheezing (odds ratio [OR] = 2.78; 95% confidence interval [CI] = 1.97-3.88 for "RSV infection"; OR = 2.61; 95% CI = 1.44-4.57 for "non-RSV respiratory infections"; and OR = 3.33; 95% CI = 2.43-4.54 for "respiratory-related disorders"). CONCLUSION: Hospitalization of children under 2 years of age for RSV infection as well as non-RSV respiratory infections and respiratory-related disorders were associated with subsequent wheezing.

BACKGROUND: Various disease prediction models have been developed, capitalizing on the wide use of electronic health records, but environmental factors that are important in the development of noncommunicable diseases are rarely included in the prediction models. Hypertensive disorders of pregnancy are leading causes of maternal morbidity and mortality and are known to cause several serious complications later in life. OBJECTIVE: This study aims to develop early hypertensive disorders of pregnancy prediction models using comprehensive environmental factors based on self-report questionnaires in early pregnancy. STUDY DESIGN: We developed machine learning and artificial intelligence models for the early prediction of hypertensive disorders of pregnancy using early pregnancy data from approximately 23,000 pregnancies in the Tohoku Medical Megabank Birth and Three Generation Cohort Study. We clarified the important features for prediction based on regression coefficients or Gini coefficients of the interpretable artificial intelligence models (i.e., logistic regression, random forest and XGBoost models) among our developed models. RESULTS: The performance of the early hypertensive disorders of pregnancy prediction models reached an area under the receiver operating characteristic curve of 0.93, demonstrating that the early hypertensive disorders of pregnancy prediction models developed in this study retain sufficient performance in hypertensive disorders of pregnancy prediction. Among the early prediction models, the best performing model was based on self-reported questionnaire data in early pregnancy (mean of 20.2 gestational weeks at filling) which consist of comprehensive lifestyles. The interpretation of the models reveals that both eating habits were dominantly important for prediction. CONCLUSION: We have developed high-performance models for early hypertensive disorders of pregnancy prediction using large-scale cohort data from the Tohoku Medical Megabank project. Our study clearly revealed that the use of comprehensive lifestyles from self-report questionnaires led us to predict hypertensive disorders of pregnancy risk at the early stages of pregnancy, which will aid early intervention to reduce the risk of hypertensive disorders of pregnancy.

BACKGROUND: Chronic kidney disease (CKD) contributes to decreased life expectancy. We examined the association between leisure-time physical activity (LTPA), non-leisure-time physical activity (non-LTPA) and kidney function. METHODS: This was a cross-sectional study including 32 162 community-dwelling adults aged ≥ 20 years from the Tohoku Medical MegaBank community-based cohort study. Kidney function was evaluated using cystatin C-based estimated glomerular filtration rate (eGFR) as well as self-reported LTPA and non-LTPA. CKD was defined as either eGFR decline (≤ 60 mL/min/1.73 m2) or presence of albuminuria (albumin-creatinine ≥ 30 mg/g). The association between domain-specific physical activity and kidney function, and CKD prevalence was examined using multivariable-adjusted ordinary least squares and modified Poisson models. RESULTS: The mean eGFR was 98.1 (± 13.2) mL/min/1.73 m2. 3 185 (9.9%) participants were classified as having CKD. The mean LTPA and non-LTPA levels were 2.9 (± 4.2) and 16.6 (± 14.2) METs-hour/day, respectively. For LTPA, in the adjusted model, the quartile groups with higher levels had a higher kidney function (β, 0.36; 95% confidence intervals [CI], [0.06, 0.66]; p = 0.019 for the 2nd quartile, β, 0.82; 95% CI, [0.51, 1.14]; p < 0.001 for the 3rd quartile, and β, 1.16; 95% CI, [0.83, 1.49]; p < 0.001 for the 4th quartile), whereas there were no apparent associations for prevalence of CKD. For non-LTPA, 4th quartile was associated with decreased eGFR (β, -0.42; 95% CI, [-0.72, -0.11]; p = 0.007) and higher prevalence of CKD prevalence (Prevalence ratio, 1.12; 95% CI, [1.02, 1.24]; p = 0.022). These associations with kidney function remained consistent in the subgroup analyses divided by demographic and biological variables. CONCLUSIONS: We observed a positive association between higher LTPA levels and better kidney function, but not association with CKD prevalence. In contrast, higher non-LTPA was negatively associated with both kidney function and CKD prevalence. These findings suggest that promoting LTPA is beneficial for kidney function.

OBJECTIVE: To investigate the inter-relationships among genetic risk, healthy lifestyle adherence, and hyperuricaemia susceptibility. METHODS: This prospective cohort study was conducted with 7,241 hyperuricaemia-free individuals aged ≥ 20 years from the Tohoku Medical Megabank Community-based cohort study. A comprehensive lifestyle score included body mass index, smoking, drinking, and physical activity, and a polygenic risk score (PRS) was constructed based on uric acid loci from a previous genome-wide association study meta-analysis. A multiple logistic regression model was used to estimate the association between genetic risk, healthy lifestyle, and hyperuricaemia incidence and calculate the area under the receiver operating characteristic curve (AUROC). Hyperuricaemia was defined as a uric acid level ≥7.0 mg/dl or a self-reported history of hyperuricaemia. RESULTS: Of the 7,241 adults (80.7% females; mean [SD] age: 57.7 [12.6] years), 217 (3.0%) developed hyperuricaemia during 3.5 years of follow-up. Genetic risk correlated with hyperuricaemia development (P for interaction = 0.287), and lifestyle risks were independently associated. Those with a high genetic risk and poor lifestyle had the highest risk (odds ratio: 5.34; 95% confidence interval [CI]: 2.61-12.10). Although not statistically significant, incorporating the PRS in the model with lifestyle information improved predictive ability (AUROC = 0.771, 95% CI: 0.736-0.806 for lifestyle; AUROC = 0.785, 95% CI: 0.751-0.819 for lifestyle and PRS; p = 0.07). CONCLUSION: : A healthy lifestyle to prevent hyperuricaemia, irrespective of genetic risk, may mitigate the genetic risk. Genetic risk may complement lifestyle factors in identifying individuals at a heightened hyperuricaemia risk.

This study aimed to investigate the association of combination of birth weight and current body mass index (BMI) with the risk of hypertension in adulthood. This cross-sectional study used data from the Tohoku Medical Megabank Community-based Cohort Study conducted in Japan. A total of 10,688 subjects aged ≥20 years were eligible. We calculated the least square (LS) means of systolic blood pressure (SBP) and trend tests were performed to evaluate the linear relationships between birth weight categories and SBP. We also used a multivariate logistic regression analysis to assess the risk of hypertension associated with the combination of birth weight and current BMI. There was a statistically inverse association between birth weight and SBP in the 20-64 age group, but no significant association in the ≥65 age group. Low birth weight (LBW) with normal BMI group had a higher risk of hypertension than the normal or high birth weight groups with normal BMI. Furthermore, the group with LBW and BMI ≥25.0 kg/m2 was the highest risk for hypertension (adjusted odds ratio: 2.73; 95% CI, 2.04-3.65) compared to the reference group (birth weight 2500-3499 g and BMI 18.5-24.9 kg/m2). There was a significant association between LBW and subsequent risk of hypertension. In addition, participants with lower birth weights had a higher risk of hypertension than those with higher birth weights. However, even in participants with a lower birth weight, the risk of hypertension could be reduced when they maintained an optimal BMI.

No study, to our knowledge, has constructed a polygenic risk score based on clinical blood pressure and investigated the association of genetic and lifestyle risks with home hypertension. We examined the associations of combined genetic and lifestyle risks with hypertension and home hypertension. In a cross-sectional study of 7027 Japanese individuals aged ≥20 years, we developed a lifestyle score based on body mass index, alcohol consumption, physical activity, and sodium-to-potassium ratio, categorized into ideal, intermediate, and poor lifestyles. A polygenic risk score was constructed with the target data (n = 1405) using publicly available genome-wide association study summary statistics from BioBank Japan. Using the test data (n = 5622), we evaluated polygenic risk score performance and examined the associations of combined genetic and lifestyle risks with hypertension and home hypertension. Hypertension and home hypertension were defined as blood pressure measured at a community-support center ≥140/90 mmHg or at home ≥135/85 mmHg, respectively, or self-reported treatment for hypertension. In the test data, 2294 and 2322 participants had hypertension and home hypertension, respectively. Both polygenic risk and lifestyle scores were independently associated with hypertension and home hypertension. Compared with those of participants with low genetic risk and an ideal lifestyle, the odds ratios for hypertension and home hypertension in the low genetic risk and poor lifestyle group were 1.94 (95% confidence interval, 1.34-2.80) and 2.15 (1.60-2.90), respectively. In summary, lifestyle is important to prevent hypertension; nevertheless, participants with high genetic risk should carefully monitor their blood pressure despite a healthy lifestyle.

INTRODUCTION: The Tohoku Medical Megabank (TMM) was established for creative reconstruction from the Great East Japan Earthquake and tsunami in 2011. Two prospective genome cohort studies in Miyagi prefecture have successfully recruited approximately 127,000 participants. The health status of these individuals was evaluated at the initial recruitment, and follow-up health checkups have been conducted every 5 years. During these health checkups, unexpected critical values were encountered, which prompted us to develop an urgent notification system. METHODS: We analyzed the frequency of critical values observed in home blood pressure (HBP) test in an urgent notification office (UNO). We returned the critical values by urgent notification before the notifications of regular results. In addition, the impact of the TMM urgent notification on the participants was evaluated. RESULTS: We issued urgent notifications of the critical values of extremely high HBP. Of the 21,061 participants who underwent HBP measurements, 256 (1.2%) met the criteria for urgent notification. It was found that abnormalities in blood sugar levels, renal function, and lipid values were frequently concurrent with the abnormal HBP readings. Annual questionnaires administered after the urgent notification, approximately 60% of those went to hospitals or clinics. CONCLUSIONS: The urgent notification system for hypertensive emergency with HBP in the TMM was well accepted by the participants and encouraged them to seek medical care. The system has been useful in addressing the prolonged healthcare problems and in promoting health care in large-scale disaster damaged areas.

Depression is comorbid with somatic diseases; however, the relationship between depressive symptoms and hypertension (HT), a risk factor for cardiovascular events, remains unclear. Home blood pressure (BP) is more reproducible and accurately predictive of cardiovascular diseases than office BP. Therefore, we focused on home BP and investigated whether depressive symptoms contributed to the future onset of home HT. This prospective cohort study used data from the Tohoku Medical Megabank Community-Cohort Study (conducted in the Miyagi Prefecture, Japan) and included participants with home normotension (systolic blood pressure (SBP) < 135 mmHg and diastolic blood pressure (DBP) < 85 mmHg). Depressive symptoms were evaluated using the Center for Epidemiologic Studies Depression Scale-Japanese version at the baseline survey. In the secondary survey, approximately 4 years later, the onset of home HT was evaluated (SBP ≥ 135 mmHg or DBP ≥ 85 mmHg) and was compared in participants with and without depressive symptoms. Of the 3 082 (mean age: 54.2 years; females: 80.9%) participants, 729 (23.7%) had depressive symptoms at the baseline survey. During the 3.5-year follow-up, 124 (17.0%) and 388 (16.5%) participants with and without depressive symptoms, respectively, developed home HT. Multivariable adjusted odds ratios were 1.37 (95% confidence interval (CI): 1.02-1.84), 1.18 (95% CI: 0.86-1.61), and 1.66 (95% CI: 1.17-2.36) for home, morning, and evening HT, respectively. This relationship was consistent in the subgroup analyses according to age, sex, BP pattern, and drinking habit. Depressive symptoms increased the risk of new-onset home HT, particularly evening HT, among individuals with home normotension. This prospective cohort study revealed that depressive symptoms are risk factors for new-onset home hypertension, particularly evening hypertension among individuals with home normotension. Assessing home blood pressure in individuals with depressive symptoms is important for the prevention of hypertension and concomitant cardiovascular diseases.

AIM: This study examined the relationship between genetic risk, healthy lifestyle, and risk of developing diabetes. METHODS: This prospective cohort study included 11,014 diabetes-free individuals ≥ 20 years old from the Tohoku Medical Megabank Community-based cohort study. Lifestyle scores, including the body mass index, smoking, physical activity, and gamma-glutamyl transferase (marker of alcohol consumption), were assigned, and participants were categorized into ideal, intermediate, and poor lifestyles. A polygenic risk score (PRS) was constructed based on the type 2 diabetes loci from the BioBank Japan study. A multiple logistic regression model was used to estimate the association between genetic risk, healthy lifestyle, and diabetes incidence and to calculate the area under the receiver operating characteristic curve (AUROC). RESULT: Of the 11,014 adults included (67.8% women; mean age [standard deviation], 59.1 [11.3] years old), 297 (2.7%) developed diabetes during a mean 4.3 (0.8) years of follow-up. Genetic and lifestyle score is independently associated with the development of diabetes. Compared with the low genetic risk and ideal lifestyle groups, the odds ratio was 3.31 for the low genetic risk and poor lifestyle group. When the PRS was integrated into a model including the lifestyle and family history, the AUROC significantly improved to 0.719 (95% confidence interval [95% CI]: 0.692-0.747) compared to a model including only the lifestyle and family history (0.703 [95% CI, 0.674-0.732]). CONCLUSION: Our findings indicate that adherence to a healthy lifestyle is important for preventing diabetes, regardless of genetic risk. In addition, genetic risk might provide information beyond lifestyle and family history to stratify individuals at high risk of developing diabetes.

AIM: To evaluate the association between housing and psychological damage caused by the Great East Japan Earthquake (GEJE) and modifiable risk factors (MRFs) of dementia for general population of older adults. METHODS: This cross-sectional study enrolled 29 039 community-dwelling older adults (mean age 69.1 ± 2.9 years, 55.5% women). We evaluated disaster-related damage (by complete or not complete housing damage) and psychological damage (by post-traumatic stress reaction [PTSR]) after the GEJE using a self-report questionnaire. MRFs encompassed the presence of depression, social isolation, physical inactivity, smoking, and diabetes. We examined the association between disaster-related damage and MRFs using ordinary least squares and modified Poisson regression models adjusted for sociodemographic and health status variables. RESULTS: Complete housing damage and PTSR were identified in 2704 (10.0%) and 855 (3.2%) individuals, respectively. The number of MRFs was significantly larger for the individuals with complete housing damage (β = 0.23; 95% confidence interval [CI]: 0.19-0.27) and PTSR (β = 0.60; 95% CI: 0.53-0.67). Prevalence ratios (PRs) for depression and physical inactivity were higher in individuals with complete housing damage. The PRs for all domains of the MRFs were significantly higher in individuals with PTSR. CONCLUSIONS: Housing and psychological damage caused by the GEJE were associated with an increased risk factor of dementia. To attenuate the risk of dementia, especially among older victims who have experienced housing and psychological damage after a disaster, multidimensional support across various aspects of MRFs is required. Geriatr Gerontol Int 2024; ••: ••-••.

BACKGROUND/AIMS: The objective of this research is to examine factors related to irritable bowel syndrome (IBS) prevalence in a large population-based study. METHODS: A cross-sectional study was conducted with participants in the Miyagi part of the Tohoku Medical Megabank Project Community-Based cohort study who completed the Rome II Modular Questionnaire. Multivariate odds ratios (ORs) for the presence of IBS and 95% confidence intervals (95% CIs) for the reference group were calculated for each factor. Additionally, a stratified analysis was performed by sex and age group (20-49 years, 50-64 years, and ≥ 65 years). RESULTS: Among 16 252 participants, 3025 (18.6%) had IBS, comprising 750 men (15.5%) and 2275 women (19.9%). Multivariate ORs for the presence of IBS decreased significantly with each year of age (OR, 0.98; 95% CI, 0.98-0.99). Moreover, compared with the reference group, ORs for the presence of IBS were significantly higher in individuals whose home was partially damaged by the Great East Japan Earthquake, those with < 16 years of education, those who spent less time walking, those with high perceived stress (1.77, 1.57-2.01), those with high psychological distress (1.58, 1.36-1.82), and those with high symptoms of depression (1.76, 1.60-1.94). In stratified analyses, a significant relationship was found between psychological factors and IBS prevalence in all sex and age groups. CONCLUSIONS: This large cross-sectional population-based cohort study identified several factors associated with IBS prevalence. Psychological factors were significantly associated with IBS prevalence across all age groups and sexes.

Recently, many phenotyping algorithms for high-throughput cohort identification have been developed. Prospective genome cohort studies are critical resources for precision medicine, but there are many hurdles in the precise cohort identification. Consequently, it is important to develop phenotyping algorithms for cohort data collection. Hypertensive disorders of pregnancy (HDP) is a leading cause of maternal morbidity and mortality. In this study, we developed, applied, and validated rule-based phenotyping algorithms of HDP. Two phenotyping algorithms, algorithms 1 and 2, were developed according to American and Japanese guidelines, and applied into 22,452 pregnant women in the Birth and Three-Generation Cohort Study of the Tohoku Medical Megabank project. To precise cohort identification, we analyzed both structured data (e.g., laboratory and physiological tests) and unstructured clinical notes. The identified subtypes of HDP were validated against reference standards. Algorithms 1 and 2 identified 7.93% and 8.08% of the subjects as having HDP, respectively, along with their HDP subtypes. Our algorithms were high performing with high positive predictive values (0.96 and 0.90 for algorithms 1 and 2, respectively). Overcoming the hurdle of precise cohort identification from large-scale cohort data collection, we achieved both developed and implemented phenotyping algorithms, and precisely identified HDP patients and their subtypes from large-scale cohort data collection.

BACKGROUND: The relationship between blood cell profiles, including hemoglobin (Hb) levels and inflammatory hematological ratios, and mental health problems currently remains unclear. AIM: This study aimed to investigate the relationship between blood cell profiles and mental health issues, including depressive state and sleep disturbance, while adjusting for potential demographic confounders. METHODOLOGY: This retrospective, cross-sectional, observational study used a population-based medical database from the Tohoku Medical Megabank Project with more than 60,000 volunteers. Data on age, sex, daily tobacco use, body mass index, and self-reported scores on the Kessler Psychological Distress Scale (K6), Athens Insomnia Scale (AIS), and the Center for Epidemiologic Studies Depression Scale (CES-D) were collected. RESULTS: A total of 62,796 volunteers (23,663 males and 39,133 females), aged ≥20 years at the time of the blood test, agreed to participate in this study. Among the evaluated blood cell profiles, Hb, hematocrit, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were significantly correlated with the K6, AIS, and CES-D scores, with strong statistical significance (p<0.0001 for all) in bivariate correlation analyses. A significant adjusted odds ratio (aOR) of the Hb level for elevated CES-D scores (aOR=0.965 [95% CI: 0.949-0.981], p<0.0001) was confirmed after adjusting for demographic data and daily tobacco use using a logistic regression model. Sensitivity analyses revealed that these associations existed in both males and females but were more prominent in the former. In male participants, a low Hb level was significantly associated with an elevated AIS score. The evaluated inflammatory hematological ratios, including NLR, PLR, and monocyte-to-lymphocyte ratio (MLR), also showed significant aORs with the K6, AIS, and CES-D scores after adjusting for demographic background. CONCLUSION: Low Hb levels and elevated inflammatory hematological ratios (NLR, MLR, and PLR) were associated with depressive state and sleep disturbances in the general population.

Risk factors for hypertension have been emphasized in the Japanese Society of Hypertension Guidelines for the Management of Hypertension. However, large-scale studies on the association of smoking, potassium excretion, and gamma-glutamyl transferase level with BP in the Japanese population are limited. We conducted a cross-sectional study to examine the association between hypertension risk factors and systolic blood pressure in the Tohoku Medical Megabank Community-based Cohort Study (23,446 men and 38,921 women aged ≥20 years). A model adjusted for age, body mass index, smoking status, drinking status, estimated daily salt intake, potassium excretion, (or urinary sodium-to-potassium ratio), gamma-glutamyl transferase, physical activity, education level, status of damage to homes during the Great East Japan Earthquake, and residential areas was used. The average age and systolic blood pressure were 62.5 (10.3) years for men and 59.6 (11.3) years for women, 128.9 (16.7) mmHg for men and 124.7 (17.5) mmHg for women, respectively. Body mass index estimated daily salt intake, urinary sodium-to-potassium ratio and gamma-glutamyl transferase levels were positively associated with systolic blood pressure. Compared with never-drinkers, current drinkers who consumed 23-45 g/day and ≥46.0 g/day had significantly increased systolic blood pressure. Conversely, current smokers (1-10 cigarettes/day and 11-20 cigarettes/day) were inversely associated with systolic blood pressure compared to never-smokers. Overall, systolic blood pressure was associated with gamma-glutamyl transferase and hypertension risk factors, including body mass index, alcohol consumption, estimated daily salt intake, urinary sodium-to-potassium ratio, and potassium excretion. Our findings support the notion that lifestyle modifications should be attempted to prevent hypertension.

BACKGROUND: The purpose of this study was to report the basic profile of the Miyagi Prefecture part of a repeated center-based survey during the second period (2nd period survey) of the Tohoku Medical Megabank Community-Based Cohort Study (TMM CommCohort Study), as well as the participants' characteristics based on their participation type in the baseline survey. METHODS: The 2nd period survey, conducted from June 2017 to March 2021, included participants of the TMM CommCohort Study (May 2013 to March 2016). In addition to the questionnaire, blood, urine, and physiological function tests were performed during the 2nd period survey. There were three main ways of participation in the baseline survey: Type 1, Type 1 additional, or Type 2 survey. The 2nd period survey was conducted in the same manner as the Type 2 survey, which was based on the community support center (CSC). RESULTS: In Miyagi Prefecture, 29,383 (57.7%) of 50,967 participants participated in the 2nd period survey. The participation rate among individuals who had visited the CSC was approximately 80%. Although some factors differed depending on the participation type in the baseline survey, the 2nd period survey respondents in the Type 1 and Type 2 survey groups at baseline had similar traits. CONCLUSIONS: The 2nd period survey of the TMM CommCohort Study provided detailed follow-up information. Following up on the health conditions of the participants will clarify the long-term effects of disasters and contribute to personalized prevention.

AIMS: Although fat mass (FM) and fat-free mass (FFM) have an impact on lipid metabolism, the relationship between different body composition phenotypes and lipid profiles is still unclear. By dividing the FM and FFM by the square of the height, respectively, the f at mass index (FMI) and fat-free mass index (FFMI) can be used to determine the variations in body composition. This study aimed to investigate the relationship of combined FMI and FFMI with low-density lipoprotein cholesterol (LDL-C) levels. METHODS: This cross-sectional study comprised 5,116 men and 13,630 women without cardiovascular disease and without treatment for hypertension, and diabetes. Following sex-specific quartile classification, FMI and FFMI were combined into 16 groups. Elevated LDL-C levels were defined as LDL-C ≥ 140 mg/dL and/or dyslipidemia treatment. Multivariable logistic regression models were used to examine the relationships between combined FMI and FFMI and elevated LDL-C levels. RESULTS: Overall, elevated LDL-C levels were found in 1,538 (30.1%) men and 5,434 (39.9%) women. In all FFMI subgroups, a higher FMI was associated with elevated LDL-C levels. Conversely, FFMI was inversely associated with elevated LDL-C levels in most FMI subgroups. Furthermore, the groups with the highest FMI and lowest FFMI had higher odds ratios for elevated LDL-C levels than those with the lowest FMI and highest FFMI. CONCLUSIONS: Regardless of FFMI, FMI was positively associated with elevated LDL-C levels. Conversely, in the majority of FMI subgroups, FFMI was inversely associated with elevated LDL-C levels.

Masked hypertension is a risk factor for cardiovascular diseases. However, masked hypertension is sometimes overlooked owing to the requirement for home blood pressure measurements for diagnosing. Mental status influences blood pressure. To reduce undiagnosed masked hypertension, this study assessed the association between depressive symptoms and masked hypertension. This cross-sectional study used data from the Tohoku Medical Megabank Project Community-Based Cohort Study (conducted in Miyagi Prefecture, Japan, from 2013) and included participants with normotension measured at the research center (systolic blood pressure<140 mmHg and diastolic blood pressure <90 mmHg). Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (Japanese version). Masked hypertension was defined as normotension measured at the research center and home hypertension (home systolic blood pressure ≥135 mmHg or home diastolic blood pressure ≥85 mmHg). The study comprised 6705 participants (mean age: 55.7 ± 13.7 years). Of these participants, 1106 (22.1%) without depressive symptoms and 393 (23.2%) with depressive symptoms were categorized to have masked hypertension. Sex-specific and age-adjusted least mean squares for home blood pressure, not for research blood pressure were significantly higher in the group with depressive symptoms in both sex categories. The multivariate odds ratio for masked hypertension in the patients with depressive symptoms was 1.72 (95% confidence interval: 1.26-2.34) in male participants and 1.30 (95% confidence interval: 1.06-1.59) in female ones. Depressive symptoms were associated with masked hypertension in individuals with normotension measured at the research center. Depressive symptoms may be one of the risk factors for masked hypertension. Depressive symptoms were associated with masked hypertension in individuals with normotension measured at research center.

AIM: The influence of family history of diabetes, probably reflecting genetic and lifestyle factors, on the association of combined genetic and lifestyle risks with diabetes is unknown. We examined these associations. METHODS: This cross-sectional study included 9,681 participants in the Tohoku Medical Megabank Community-based Cohort Study. A lifestyle score, which was categorized into ideal, intermediate, and poor lifestyles, was given. Family history was obtained through a self-reported questionnaire. A polygenic risk score (PRS) was constructed in the target data (n=1,936) using publicly available genome-wide association study summary statistics from BioBank Japan. For test data (n=7,745), we evaluated PRS performance and examined the associations of combined family history and genetic and lifestyle risks with diabetes. Diabetes was defined as non-fasting blood glucose ≥ 200 mmHg, HbA1c ≥ 6.5%, and/or self-reported diabetes treatment. RESULTS: In test data, 467 (6.0%) participants had diabetes. Compared with a low genetic risk and an ideal lifestyle without a family history, the odds ratio (OR) was 3.73 (95% confidence interval [CI], 1.92-7.00) for a lower genetic risk and a poor lifestyle without a family history. Family history was significantly associated with diabetes (OR, 3.58 [95% CI, 1.73-6.98]), even in those with a low genetic risk and an ideal lifestyle. Even among participants who had an ideal lifestyle without a family history, a high genetic risk was associated with diabetes (OR, 2.49 [95% CI, 1.65-3.85]). Adding PRS to family history and conventional lifestyle risk factors improved the prediction ability for diabetes. CONCLUSIONS: Our findings support the notion that a healthy lifestyle is important to prevent diabetes regardless of genetic risk.

BACKGROUND: Low birth weight (LBW) is a leading cause of neonatal morbidity and mortality, and increases various disease risks across life stages. Prediction models of LBW have been developed before, but have limitations including small sample sizes, absence of genetic factors and no stratification of neonate into preterm and term birth groups. In this study, we challenged the development of early prediction models of LBW based on environmental and genetic factors in preterm and term birth groups, and clarified influential variables for LBW prediction. METHODS: We selected 22,711 neonates, their 21,581 mothers and 8,593 fathers from the Tohoku Medical Megabank Project Birth and Three-Generation cohort study. To establish early prediction models of LBW for preterm birth and term birth groups, we trained AI-based models using genetic and environmental factors of lifestyles. We then clarified influential environmental and genetic factors for predicting LBW in the term and preterm groups. RESULTS: We identified 2,327 (10.22%) LBW neonates consisting of 1,077 preterm births and 1,248 term births. Our early prediction models archived the area under curve 0.96 and 0.95 for term LBW and preterm LBW models, respectively. We revealed that environmental factors regarding eating habits and genetic features related to fetal growth were influential for predicting LBW in the term LBW model. On the other hand, we identified that genomic features related to toll-like receptor regulations and infection reactions are influential genetic factors for prediction in the preterm LBW model. CONCLUSIONS: We developed precise early prediction models of LBW based on lifestyle factors in the term birth group and genetic factors in the preterm birth group. Because of its accuracy and generalisability, our prediction model could contribute to risk assessment of LBW in the early stage of pregnancy and control LBW risk in the term birth group. Our prediction model could also contribute to precise prediction of LBW based on genetic factors in the preterm birth group. We then identified parental genetic and maternal environmental factors during pregnancy influencing LBW prediction, which are major targets for understanding the LBW to address serious burdens on newborns' health throughout life.

A system for inputting and storing family information, named “BirThree Enrollment,” was developed to promote a birth and three-generation cohort study (BirThree Cohort Study). In this cohort study, it was necessary to satisfy many operational demands while constantly overwriting and changing input information. Complex kinship information must be quickly and accurately inputed and corrected, and information on those families not yet recruited must be retrieved. For these purposes, many devices are needed, from an input interface to the internal data structure. In the field of genetic statistics, a simple standard expressive form (describe father-child relation and mother-child relation) is used for describing family structure. However, this form doesn't have sufficient information. So we developed a new form in conducting the BirThree Cohort Study. Hence, we expanded the data structure, and constructed the Input control system. Family pedigree information is stored along with initial clinical information, and this enabled the input of all self-reported information to the data base. Operators are able to input this family information before the day is out. As a result, when recruitment is completed, family information will be completed concurrently. Therefore, operators can immediately know certain person's family structure. In this model data correction was improved dramatically, and the system was operated successfully. This study is the first report of the method for storing three generations of family data.

BACKGROUND: Although live-attenuated vaccines are contraindicated under immunosuppression, the immune status of patients with inflammatory bowel disease (IBD) has not been fully assessed prior to immunosuppressive therapy. AIMS: To investigate antiviral serostatus against viruses requiring live vaccines for prevention in IBD patients undergoing immunosuppressive therapy. METHODS: This multicenter study included IBD patients who were aged <40 years and were treated with thiopurine monotherapy, molecular-targeted monotherapy, or combination therapy. Gender- and age-matched healthy subjects (HS) living in the same areas were included as control group. Antibody titers against measles, rubella, mumps, and varicella were measured by enzyme-linked immunosorbent assays. RESULTS: A total of 437 IBD patients (163 ulcerative colitis [UC] and 274 Crohn's disease [CD]) and 225 HS were included in the final analysis. Compared with HS, IBD patients had lower seropositivity rates for measles (IBD vs. HS = 83.91% vs. 85.33%), rubella (77.55% vs. 84.89%), mumps (37.50% vs. 37.78%), and varicella (91.26% vs. 96.44%). Gender- and age-adjusted seropositivity rates were lower in UC patients than in both CD patients and HS for measles (UC, CD, and HS = 81.60%, 85.29%, and 85.33%), rubella (76.40%, 78.23%, and 84.89%), mumps (27.16%, 43.70%, and 37.78%), and varicella (90.80%, 91.54%, and 96.44%); the difference was significant for all viruses except measles. Divided by the degree of immunosuppression, there were no significant differences in seropositivity rates among IBD patients. CONCLUSIONS: IBD patients, especially those with UC, exhibit reduced seropositivity rates and may benefit from screening prior to the initiation of immunosuppressive therapy.

To reveal gene-environment interactions underlying common diseases and estimate the risk for common diseases, the Tohoku Medical Megabank (TMM) project has conducted prospective cohort studies and genomic and multiomics analyses. To establish an integrated biobank, we developed an integrated database called "dbTMM" that incorporates both the individual cohort/clinical data and the genome/multiomics data of 157,191 participants in the Tohoku Medical Megabank project. To our knowledge, dbTMM is the first database to store individual whole-genome data on a variant-by-variant basis as well as cohort/clinical data for over one hundred thousand participants in a prospective cohort study. dbTMM enables us to stratify our cohort by both genome-wide genetic factors and environmental factors, and it provides a research and development platform that enables prospective analysis of large-scale data from genome cohorts.

Human biomedical datasets that are critical for research and clinical studies to benefit human health also often contain sensitive or potentially identifying information of individual participants. Thus, care must be taken when they are processed and made available to comply with ethical and regulatory frameworks and informed consent data conditions. To enable and streamline data access for these biomedical datasets, the Global Alliance for Genomics and Health (GA4GH) Data Use and Researcher Identities (DURI) work stream developed and approved the Data Use Ontology (DUO) standard. DUO is a hierarchical vocabulary of human and machine-readable data use terms that consistently and unambiguously represents a dataset's allowable data uses. DUO has been implemented by major international stakeholders such as the Broad and Sanger Institutes and is currently used in annotation of over 200,000 datasets worldwide. Using DUO in data management and access facilitates researchers' discovery and access of relevant datasets. DUO annotations increase the FAIRness of datasets and support data linkages using common data use profiles when integrating the data for secondary analyses. DUO is implemented in the Web Ontology Language (OWL) and, to increase community awareness and engagement, hosted in an open, centralized GitHub repository. DUO, together with the GA4GH Passport standard, offers a new, efficient, and streamlined data authorization and access framework that has enabled increased sharing of biomedical datasets worldwide.