Social and gene interactions to understand the risk of gestational diabetes mellitus

社会和基因相互作用以了解妊娠糖尿病的风险

• 批准号: 10463650
• 负责人: Takeo Fujiwara
• 金额: $ 20.99万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-06 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10463650
• 关键词: Accounting; Address; Affect; Anthropometry; Asian; Asian Americans; Behavioral; Beta Cell; Birth; Birth trauma; Blood Glucose; Body mass index; CDKN2A gene; Cardiovascular Diseases; Cell physiology; Cesarean section; Clinical Data; Cohort Studies; Complex; Data; Development; Diet; Environmental Exposure; Environmental Risk Factor; Epidemiology; Ethnic Origin; Etiology; Family history of; Fetus; Gene Expression; Generations; Genes; Genetic; Genetic Polymorphism; Genetic Risk; Genotype; Gestational Diabetes; Glucose; Individual; Infant; Infrastructure; Japan; Japanese; Lead; Life Style; Low Prevalence; Maternal Age; Medical; Medical Genetics; Medical Records; Metabolic Diseases; Morbidity - disease rate; Mothers; Neonatal Hypoglycemia; Newborn Infant; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Persons; Physical activity; Physiology; Placenta; Play; Pre-Eclampsia; Predisposition; Pregnancy; Pregnancy Complications; Pregnant Women; Prevalence; Prevention; Publishing; Questionnaires; Race; Research; Research Personnel; Risk; Risk Factors; Role; Single Nucleotide Polymorphism; Social Interaction; Social support; Socioeconomic Status; Testing; United States; Woman; base; cohort; dietary; disorder risk; fetal; gene environment interaction; gene interaction; genetic makeup; genome wide association study; genome-wide; high risk population; improved; innovation; insight; lifestyle factors; lifestyle intervention; long-term sequelae; novel; offspring; personalized approach; precision medicine; prevent; preventive intervention; protective factors; sedentary lifestyle; sleep pattern; social; social capital; social determinants; social factors; tv watching; waist circumference

PROJECT SUMMARY/ABSTRACT Gestational diabetes mellitus (GDM) is a risk factor for pregnancy complications and long-term morbidities affecting both women with the condition and their offspring. Asian women are disproportionately impacted by GDM but tend to have a lower prevalence of obesity, suggesting the possibility of a genetic or lifestyle predisposition in this group. We have the unique opportunity to use high-quality epidemiological, clinical and genetic data from a large Japanese cohort of ~22,000 pregnant women that could provide valuable insight regarding the etiology of GDM, including the interaction of lifestyle and genetic factors that play important roles in pregnancy-induced adaptation of glucose physiology. Independent of genetics, lifestyle factors (e.g., diet, physical activity) and social factors (e.g., social support, social capital) have been found to be predictors of GDM. Estimation of the effects of different levels of social, lifestyle, or behavioral factors in different genotypes could ultimately inform the personalization of lifestyle interventions to a person’s genetic makeup to prevent GDM. However, we could find only two studies on the association between genotypes and GDM and none on interactions between genetics and lifestyle or social determinants on the development of GDM, making this study highly innovative. To investigate such interactions, we will leverage already collected single nucleotide polymorphism (SNP) data from the Tohoku Medical Megabank Birth and Three-Generation Cohort Study: 1) to examine how genotypes of mothers and their fetuses modify the effects of lifestyle/behavioral factors (e.g., physical activity, sedentary behavior, dietary quality, sleep patterns, screen time) and anthropometry (e.g., BMI, waist circumference) on the risk of developing GDM in pregnant women (Aim 1), and 2) to examine how particular genotypes of mothers and fetuses modify the effects of social factors (e.g., social support/networks, social capital, socio-economic status) on the risk of developing GDM among pregnant women (Aim 2). We will first conduct a genome-wide association study (GWAS) using genome-wide SNP data to assess associations between each individual SNP and the risk of GDM, while accounting for relatedness between mother-infant dyads (and mothers and other relatives). We will also develop a novel genome-wide polygenic score for GDM, based on prior studies and maternal and fetal SNPs we identify (by assessing whether the existing score can be improved by adding or removing SNPs). Finally, while also taking into account relatedness, we will analyze associations between genotypes, lifestyle/behavioral and social factors, and GDM risk, specifically by conducting gene-environment interaction analyses to examine how particular genotypes modify the effects of specific lifestyle/behavioral and social factors on the risk of GDM. We expect to identify genetic and environmental risk factors that can inform “precision medicine” treatment approaches (i.e., personalized preventive interventions for GDM) to contribute to the prevention of GDM and its sequelae.

项目摘要/摘要 胎儿糖尿病（GDM）是妊娠并发症和长期病毒的危险因素 影响有这种疾病及其后代的妇女。亚洲妇女受到不成比例的影响 GDM，但肥胖的患病率较低，表明遗传或生活方式的可能性 该组中的易感性。我们有独特的机会使用高质量的流行病学，临床和 来自大约22,000名孕妇的日本大型孕妇的遗传数据，这些数据可以提供宝贵的见解 关于GDM的病因，包括生活方式的相互作用和起着重要作用的遗传因素 在怀孕引起的葡萄糖生理适应。独立于遗传学，生活方式因素（例如饮食， 身体活动）和社会因素（例如，社会支持，社会资本）是 GDM。估计不同基因型中不同社会，生活方式或行为因素的影响的影响 最终可以为一个人的遗传构成的生活方式干预措施的个性化，以防止 GDM。但是，我们只能找到有关基因型与GDM之间关联的两项研究，没有关于 遗传学与生活方式或社会决定者在GDM的发展中的互动，使这 研究高度创新。为了研究这种相互作用，我们将利用已经收集的单核苷酸 来自Tohoku Medical Megabank出生和三代队列研究的多态性（SNP）数据：1） 检查母亲及其胎儿的基因型如何改变生活方式/行为因素的影响（例如， 体育锻炼，久坐行为，饮食质量，睡眠方式，屏幕时间）和人体测量法（例如， BMI，腰圈）关于孕妇患GDM的风险（AIM 1），以及2） 母亲和胎儿的特定基因型改变了社会因素的影响（例如，社会支持/网络， 社会资本，社会经济地位）关于在孕妇中发展GDM的风险（AIM 2）。我们将 首先使用全基因组SNP数据进行全基因组关联研究（GWAS）来评估关联 在每个单独的SNP和GDM的风险之间，同时考虑母亲之间的相关性 二元（以及母亲和其他亲戚）。我们还将为GDM开发一个新的全基因组多基因评分 根据先前的研究以及母亲和胎儿SNP，我们确定（通过评估现有分数是否可以 通过添加或删除SNP可以改进）。最后，同时还考虑了相关性，我们将分析 基因型，生活方式/行为和社会因素以及GDM风险之间的关联，特别是 进行基因环境相互作用分析，以检查特定基因型如何改变 针对GDM风险的特定生活方式/行为和社会因素。我们希望识别遗传和 可以告知“精密医学”治疗方法的环境风险因素（即个性化 GDM的预防干预措施有助于预防GDM及其后遗症。