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Abstract

Click to add/remove this article to your list of 'My Favorites' A GWAS of Adiposity Measures in African Americans: The IRAS Family Study

Year: 2009

Abstract Number: 1741-P

Authors: MARIA R. WING*, MATTHEW E. TALBERT*, NICHOLETTE D. PALMER, JULIE T. ZIEGLER, TALIN HARITUNIANS, KENT D. TAYLOR, CARL D. LANGEFELD, MICHAEL BRYER-ASH, DONALD W. BOWDEN

Institutions: Winston-Salem, NC, Los Angeles, CA, Oklahoma City, OK

Results: African-Americans have higher rates of obesity and diabetes. To investigate the genetic determinants of obesity, the IRAS Family Study has performed a pilot-level genome-wide association study (GWAS) for adiposity in our African American cohort. A total of 254 individuals were genotyped on the Affy 6.0 platform with 692,923 autosomal SNPs passing quality control (>5% MAF, >95% call rate, HWE P>10-4 & consistent with Mendelian inheritance). Preliminary analysis using a linear regression on residuals adjusting for familial correlation under the additive model revealed strong genic associations with Body Mass Index (BMI) and abdominal CT-derived measures of visceral and subcutaneous adipose tissue (VAT; SAT) and visceral to subcutaneous ratio (VSR). Strongest association was seen with BMI (P<2.0E-8), with slightly larger p-values observed for SAT (P<6.6E-7), BMI-adjusted VAT (P<2.4E-7), and BMI-adjusted VSR (P<1.7E-7). Significant variant associations in functionally relevant genes were seen with several adiposity traits. A SNP in CYP19A1 was associated with BMI (P=5.1E-7), while 1 SNP in TBC1D29 (P=9.3E-6) was associated with SAT. Additionally, 2 SNPs in TMEFF2 were associated with both BMI and SAT (P<3.6E-6). The most significant SNPs were located in coding regions for BMI-adjusted VAT in FETUB (P=2.4E-7) and for BMI-adjusted VSR in MYO18B (P=1.7E-7). Slightly larger BMI-adjusted VAT p-values were also seen for SNPs in STAT3 (P=1.7E-6) and PTPRD (P= 3.1E-6). Other SNPs associated with BMI-adjusted VSR were observed in the genes IQGAP1 (P=2.2E-6) and PDSS2 (P=2.3E-6). Completion of the GWAS in the IRASFS African Americans will illuminate the genetic determinants of adiposity in ethnic minorities. In conclusion, many of the above associated genes have physiologic links to adiposity, strongly supporting the significance of these findings in African Americans. *Both authors contributed equally to this work

Category: Obesity - Human