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: 10218486
• 负责人: Takeo Fujiwara
• 金额: $ 18.56万
• 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 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10218486
• 关键词: Accounting; Address; Affect; Anthropometry; Asian Americans; Asians; 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 Population; 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; 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.

项目总结/摘要 妊娠期糖尿病（GDM）是妊娠并发症和长期发病的危险因素 影响到患病的女性和她们的后代亚洲女性受到的影响不成比例 但GDM的肥胖患病率往往较低，提示可能与遗传或生活方式有关 在这个群体中。我们有独特的机会使用高质量的流行病学，临床和 来自日本约22，000名孕妇的大型队列的遗传数据，可以提供有价值的见解 关于GDM的病因，包括生活方式和遗传因素的相互作用，发挥重要作用， 在妊娠诱导的葡萄糖生理适应中的作用。与遗传学无关，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）被发现是 GDM。估计不同基因型中不同水平的社会、生活方式或行为因素的影响 最终可以告知个性化的生活方式干预一个人的基因组成，以防止 GDM。然而，我们发现只有两项研究是关于基因型与GDM之间的关联， 遗传学和生活方式或社会决定因素对GDM发展的相互作用， 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， 来自东北医疗Megabank出生和三代队列研究的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， 身体活动、久坐行为、饮食质量、睡眠模式、屏幕时间）和人体测量（例如， 体重指数，腰围）对孕妇发生GDM的风险（目的1），和2）检查如何 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）对孕妇发生GDM风险的影响（目标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）以评估关联 每个SNP与GDM风险之间的关系，同时考虑母婴之间的相关性， 二人组（以及母亲和其他亲属）。我们还将开发一种新的GDM全基因组多基因评分， 基于先前的研究和母亲和胎儿的SNPs，我们确定（通过评估现有的分数是否可以 通过添加或去除SNP来改善）。最后，在考虑相关性的同时，我们将分析 基因型、生活方式/行为和社会因素与GDM风险之间的关联，特别是通过 进行基因-环境相互作用分析，以研究特定基因型如何改变 具体的生活方式/行为和社会因素对GDM的风险。我们希望能找出基因和 可以告知“精确医学”治疗方法的环境风险因素（即，个性化 GDM的预防性干预），以促进GDM及其后遗症的预防。