Association of circulating metabolites and polygenic risk score with incident type 2 diabetes: a prospective community-based cohort study.

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.

Associations of family history of hypertension, genetic, and lifestyle risks with incident hypertension.

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.

Unraveling the Trajectories from Health to Disease Onset Using Health Checkup Data.

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.

Development of AI Models for Early Prediction of Preterm Birth.

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.

Comparison of genotypes and phenotypes for von Willebrand factor gene variants using Japanese genome database.

von Willebrand disease (VWD) is a common inherited bleeding disorder. The aim of this study was to determine the predicted disease states associated with various pathogenic von Willebrand factor (VWF) variants and their phenotypes using the largest Japanese whole-genome database. Of the 5857 gene variants registered in the Japanese Multi-Omics Reference Panel (jMorp), variants with the following criteria were extracted: (1) caused protein abnormalities due to genetic alterations; (2) have already been detected and included in a database, including known association with VWD; and (3) highly likely pathogenic by in silico analysis.

Household income modifies the association between social capital and gestational diabetes mellitus in Japan: Results from TMM BirThree Cohort Study.

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.

Genome-Wide Association Study of Intraocular Pressure in Population-Based Cohorts in Japan: The Tohoku Medical Megabank Organization Eye Study.

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.

Respiratory syncytial virus infection, non-respiratory syncytial virus respiratory infections, and later wheezing.

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).

Linking international registries to FHIR and Phenopackets with RareLink: a scalable REDCap-based framework for rare disease data interoperability.

While Research Electronic Data Capture (REDCap) has been widely adopted in rare disease research, its unconstrained data format often leads to implementations that lack native interoperability with global health data standards, limiting secondary data use. To address this, we developed and validated , an open-source framework implementing our previously-published ontology-based rare disease common data model, enabling standardised data exchange between REDCap, international registries, and downstream analysis tools. Its preconfigured pipelines interact with the local REDCap application programming interface and enable semi-automatic import or export of data to the Global Alliance for Genomics and Health (GA4GH) Phenopackets and Health Level 7 (HL7) Fast Healthcare Interoperability Resources (FHIR) instances, conforming to the HL7 International Patient Summary and Genomics Reporting profiles.

Autoantibodies against endothelial protein C receptor and integrin αvβ6 predict the development of ulcerative colitis.

Background: A method for predicting ulcerative colitis (UC) onset has not been established. Serum autoantibodies have been suggested as potential predictive biomarkers for UC onset. We aimed to validate the risks associated with serological and environmental factors and construct a model for predicting UC development.

Integration of Digital Phenotyping and Genomics for Dry Eye Disease: Protocol for a Prospective Cohort Study.

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.

Prevalence and Associations of Epiretinal Membrane by OCT in a Japanese Population-Based Cohort: Tohoku Medical Megabank Organization Eye Study.

Purpose: To examine the prevalence of epiretinal membrane (ERM) according to the OCT-based severity scales, and to describe associations focusing on the impact of smoking and axial length of the globe.

Design: Cross-sectional study.

Participants: The baseline examination cohort comprised participants from the Tohoku Medical Megabank community cohort recruited from 2013 to 2017.

Exploring the association between human breast milk lipids and early adiposity rebound in children: A case-control study.

Objectives: Adiposity rebound (AR) corresponds to the start of the second rise in the body mass index curve during infant growth. Early AR (before age 5) confers increased risk of adiposity and metabolic disorders but is less likely to occur in breastfed infants. Although lipids in breast milk are important in child growth, information is limited regarding which lipids are involved in AR.

Has the impact of cigarette smoking on mortality been underestimated by overlooking second-hand smoke? Tohoku medical megabank community-based cohort study.

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.

Sex difference in genetic risk in the prevalence of atrial fibrillation.

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.

Genetic effects on gestational diabetes mellitus and their interactions with environmental factors among Japanese women.

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.

Consistent Performance of GPT-4o in Rare Disease Diagnosis Across Nine Languages and 4967 Cases.

Background: Large language models (LLMs) are increasingly used in the medical field for diverse applications including differential diagnostic support. The estimated training data used to create LLMs such as the Generative Pretrained Transformer (GPT) predominantly consist of English-language texts, but LLMs could be used across the globe to support diagnostics if language barriers could be overcome. Initial pilot studies on the utility of LLMs for differential diagnosis in languages other than English have shown promise, but a large-scale assessment on the relative performance of these models in a variety of European and non-European languages on a comprehensive corpus of challenging rare-disease cases is lacking.

Association Between Human Milk Oligosaccharides and Early Adiposity Rebound in Children: A Case-Control Study of the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

Background: Adiposity rebound (AR) is the point when the BMI begins to rise again during early childhood. Early AR (before age 5) is associated with higher risk of lifelong obesity and metabolic disorders and may be influenced by breastfeeding. Although human milk oligosaccharides (HMOs) in breast milk are crucial for child growth, their association with AR status has not been studied.

Returning genetic risk information for hereditary cancers to participants in a population-based cohort study in Japan.

Large-scale population cohort studies that collect genomic information are tasked with returning an assessment of genetic risk for hereditary cancers to participants. While several studies have applied to return identified genetic risks to participants, comprehensive surveys of participants' understanding, feelings, and behaviors toward cancer risk remain to be conducted. Here, we report our experience and surveys of returning genetic risks to 100 carriers of pathogenic variants for hereditary cancers identified through whole genome sequencing of 50 000 individuals from the Tohoku Medical Megabank project, a population cohort study.

Association Between Sodium- and Potassium-Related Urinary Markers and the Prevalence of Atrial Fibrillation.

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.

Absolute quantification of eight human milk oligosaccharides in breast milk to evaluate their concentration profiles and associations with infants' neurodevelopmental outcomes.

Human milk oligosaccharides (HMOs) have been positively associated with child neurodevelopment in some cohort studies. However, there is a lack of consistency in the association between HMOs and benefits to infants' brains. Moreover, the quantification methods for HMOs have not yet been standardized.

Early prediction of hypertensive disorders of pregnancy toward preventive early intervention.

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.

Associations between leisure time, non-leisure time physical activity, and kidney function in Japanese adults: a cross-sectional study.

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.