Genetic Determinants of Adiposity in African Americans

描述(申请人提供)：非裔美国人常见疾病的一个主要风险因素是肥胖，肥胖发生在45%的成年人口中。到目前为止，人们对导致这一人群肥胖和肥胖的基因因素知之甚少。我们对1760名非裔美国人进行了一项关于体重指数(BMI)的全基因组关联研究，该研究源于一项名为R01DK663581的研究--“非裔美国人2型糖尿病的遗传学”。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之前在欧洲人衍生的人群中发现的基因因素有很大不同。因此，在非裔美国人中识别影响肥胖和肥胖的基因位点可能为肥胖的调节找到新的途径，这是许多复杂疾病的有力预测因素，包括心脏代谢性疾病和癌症等。这些目标将通过执行以下特定目标来实现。1.对全球气候变化数据进行全面分析。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)研究和健康老龄化与身体成分(Health ABC)研究的GWAs数据进行荟萃分析，该研究包含多达11000个样本。3.AIMS 1和AIMS 2中高分SNPs的基因分型，以及来自欧洲GWAS研究的6000个样本中的确认基因座。4.对有强有力证据表明与非裔美国人体重指数相关的基因进行跟踪，进行密集的生物信息学和测序分析，以深入了解它们在肥胖调节中的作用以及与心脏代谢性疾病的关联。这些目标的成功完成将为未来在分子、细胞和生物水平上研究这些基因座的作用机制奠定基础，从而为预测、预防和治疗非裔美国人肥胖的长期目标做出贡献。 公共卫生相关性：这项研究的重点是确定导致非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.