Genetic Determinants of Adiposity in African Americans

描述（由申请人提供）：非裔美国人常见疾病的主要风险因素是肥胖，45%的成年人患有肥胖。迄今为止，人们对这一人群中肥胖和肥胖的遗传因素知之甚少。我们对来自2型糖尿病（T2DM）研究R01 DK663581“非裔美国人2型糖尿病遗传学”的1760名非裔美国人进行了体重指数（BMI）的全基因组关联研究（GWAS）。我们最初的GWAS结果表明，影响非裔美国人肥胖的遗传因素似乎与以前在欧洲来源的人群中发现的遗传因素有很大不同。因此，在非洲裔美国人中影响肥胖和肥胖的基因位点的鉴定可以确定用于调节肥胖的新途径，这是许多复杂疾病包括心脏代谢疾病和癌症等的强有力的预测因子。这些目标将通过执行以下具体目标来实现。1.对GWAS数据进行全面分析。2.对来自维克森林大学医学院（WFUSM）研究、候选基因关联资源（CARe）研究和健康老化和身体成分（健康ABC）研究的GWAS数据进行Meta分析，这些研究包括多达11000个样本。3.来自目标1和2的基因型高得分SNP，以及来自欧洲GWAS研究的6000个样本的确认基因座。4.跟踪有强有力证据表明与非裔美国人BMI相关的基因座，进行密集的生物信息学和测序分析，以深入了解其在肥胖调节中的作用以及与心脏代谢疾病的相关性。这些目标的成功完成将为未来在分子、细胞和生物体水平上研究这些位点的作用机制奠定基础，从而有助于实现预测、预防和治疗非裔美国人肥胖症的长期目标。 公共卫生相关性：这项研究的重点是确定非洲裔美国人肥胖的基因。

DESCRIPTION (provided by applicant): A major risk factor for common diseases n the African American population is obesity, which occurs in 45% of the adult population. To date little is known about the genetic contributors to adiposity and obesity in this population. We have performed a genome-wide association study (GWAS) on body mass index (BMI) in 1760 African Americans derived from a type 2 diabetes (T2DM) study R01 DK663581 "Genetics of African American Type 2 Diabetes". Our initial GWAS results suggest that genetic factors affecting adiposity in African Americans appear to be largely different from those previously identified in European-derived populations. Thus, identification of genetic loci affecting adiposity and obesity in African Americans may identify novel pathways for regulation of adiposity, which is a strong predictor for many complex diseases including cardiometabolic diseases and cancer, etc. These goals will be met by performing the following specific aims. 1. Carry out a comprehensive analysis of the GWAS data. 2. Perform meta analysis of GWAS data from the Wake Forest University School of Medicine (WFUSM) Study, the Candidate Gene Association Resource (CARe) Study and the Health Aging and Body Composition (Health ABC) Study consisting of up to 11000 samples. 3. Genotype high scoring SNPs from Aims 1 and 2, as well as confirm loci from European GWAS studies in 6000 samples. 4. Follow up loci with strong evidence of association with BMI in African Americans for intensive bioinformatics and sequencing analyses to gain insights on their roles in adiposity regulation and association with cardiometabolic diseases. Successful completion of these aims will set the stage for future studies on the mechanisms of action of these loci at molecular, cellular, and organism levels to contribute to the long term goal on the prediction, prevention, and treatment of obesity in African Americans. PUBLIC HEALTH RELEVANCE: This study is focused on identifying genes that ontribute to adiposity in the African American population.