Gene-Environment Interactions and Weight Gain

描述（由申请人提供）：拟议研究的目的是研究基因、环境和基因-环境相互作用如何影响生命周期脆弱时期体重指数（BMI）的时间变化。对于个体对环境环境的易感性如何影响达到的尺寸和体重变化轨迹，我们知之甚少。我们将利用弗雷明汉心脏研究全基因组关联研究（GWAS）的数据，在两项由nih资助的高肥胖发生率纵向队列研究中，调查遗传变异和可改变环境因素在决定体重方面的相互作用：全国青少年健康纵向研究（Add Health）是1994年在美国上学的青少年的全国代表性样本，随访12年，包括5,000名欧洲美国人，2,100名非洲裔美国人，1,500名西班牙裔美国人和900名亚裔美国人；宿务纵向健康和营养调查（CLHNS），对1800名育龄妇女进行了20年的随访，我们将利用这一队列来扩大亚洲样本，并比较不同环境下的结果。这两个数据集都提供了个人、家庭和社区层面的详细纵向数据，并为广泛的基因分型提供了足够的DNA。单核苷酸多态性（SNP）选择将基于：1)来自Framingham心脏研究的GWAS数据，与BMI水平和变化相关的SNP证据最多；2)基于文学的候选人。在基因分型的第一阶段，我们将在Add Health欧美样本的子样本中选择大约7300个snp进行关联测试。在第二阶段，我们将在欧洲、非洲、西班牙裔和亚裔美国人Add Health亚样本和CLHNS样本中，对来自第一阶段的大约1200个相关性最强的snp进行基因分型。预测BMI水平和变化的环境因素、行为和基因将在每个队列中进行识别，然后在预测BMI随时间变化的统计模型中评估基因与环境的相互作用。我们的研究将进一步了解遗传变异的影响是如何被环境所改变的，这是制定预防和治疗肥胖的有效方案的关键一步，也是减少种族/民族和社会经济地位在肥胖方面的差异的关键一步。公共卫生相关性：本研究的目的是研究基因、环境和基因-环境相互作用如何影响生命周期脆弱时期体重指数（BMI）的时间变化。我们的研究将进一步了解遗传变异的影响是如何被环境所改变的，这是制定预防和治疗肥胖的有效方案的关键一步，也是减少种族/民族和社会经济地位在肥胖方面的差异的关键一步。

DESCRIPTION (provided by applicant): The objective of the proposed research is to investigate how genes, environment, and gene-environment interactions influence temporal changes in body mass index (BMI) at vulnerable periods of the life cycle. Little is known about how individual susceptibility to environmental contexts influences attained size and trajectories of body mass change. We will leverage Framingham Heart Study genome-wide association study (GWAS) data to investigate interactions between genetic variation and modifiable environmental factors in the determination of body mass in two NIH-funded longitudinal cohort studies with high obesity incidence: The National Longitudinal Study of Adolescent Health (Add Health), a nationally representative sample of adolescents attending US schools in 1994 with 12 years of follow-up, including 5,000 European Americans, 2,100 African Americans, 1,500 Hispanic Americans and 900 Asian Americans; and the Cebu Longitudinal Health and Nutrition Survey (CLHNS), a cohort of 1,800 reproductive aged women with 20 years of follow up, which we will use to augment the Asian sample and to compare results across different environments. Both datasets provide detailed longitudinal data at individual, household, and community levels and sufficient DNA for extensive genotyping. Single nucleotide polymorphisms (SNP) selection will be based on: 1) GWAS data from the Framingham Heart Study, SNPs with greatest evidence for association with BMI level and change; and 2) literature-based candidates. In the first stage of genotyping, we will select approximately 7,300 SNPs for association testing in a subsample of the Add Health European-American sample. In a second stage, we will genotype approximately 1,200 of the most strongly associated SNPs from stage 1 in the rest of the European, African, Hispanic, and Asian American Add Health subsamples and in the CLHNS sample. Environmental factors, behaviors and genes that predict BMI level and change will be identified in each cohort, and then gene by environment interactions will be assessed in statistical models predicting BMI over time. Our study will further the understanding of how the effects of genetic variation are modified by the environment, a critical step towards development of efficacious programs for the prevention and treatment of obesity and the reduction of disparities in obesity by race/ethnicity and socioeconomic status. PUBLIC HEALTH RELEVANCE: The objective of the proposed research is to investigate how genes, environment, and gene-environment interactions influence temporal changes in body mass index (BMI) at vulnerable periods of the life cycle. Our study will further the understanding of how the effects of genetic variation are modified by the environment, a critical step towards development of efficacious programs for the prevention and treatment of obesity and the reduction of disparities in obesity by race/ethnicity and socioeconomic status.