Genome‐wide Association Study and Follow‐up Analysis of Adiposity Traits in Hispanic Americans: The IRAS Family Study |
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| Authors: | Jill M. Norris Carl D. Langefeld Matthew E. Talbert Maria R. Wing Talin Haritunians Tasha E. Fingerlin Anthony J.G. Hanley Julie T. Ziegler Kent D. Taylor Steven M. Haffner Yii‐Der I. Chen Donald W. Bowden Lynne E. Wagenknecht |
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| Affiliation: | 1. Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado, USA;2. Division of Public Health Sciences, Wake Forest University School of Medicine, Winston‐Salem, North Carolina, USA;3. Department of Biochemistry, Wake Forest University School of Medicine, Winston Salem, North Carolina, USA;4. Center for Human Genomics, Wake Forest University School of Medicine, Winston‐Salem, North Carolina, USA;5. Medical Genetics Institute, Burns and Allen Cedars‐Sinai Research Institute, Los Angeles, California, USA;6. Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada;7. Department of Medicine, University of Texas Health Sciences Center at San Antonio, San Antonio, Texas, USA;8. Center for Diabetes Research, Wake Forest University School of Medicine, Winston‐Salem, North Carolina, USA |
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| Abstract: | We investigated candidate genomic regions associated with computed tomography (CT)–derived measures of adiposity in Hispanics from the Insulin Resistance Atherosclerosis Study Family Study (IRASFS). In 1,190 Hispanic individuals from 92 families 3 from the San Luis Valley, Colorado and San Antonio, Texas, we measured CT‐derived visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and visceral:subcutaneous ratio (VSR). A genome‐wide association study (GWAS) was completed using the Illumina HumanHap 300 BeadChip (～317K single‐nucleotide polymorphisms (SNPs)) in 229 individuals from the San Antonio site (stage 1). In total, 297 SNPs with evidence for association with VAT, SAT, or VSR, adjusting for age and sex (P < 0.001), were genotyped in the remaining 961 Hispanic samples. The entire Hispanic cohort (n = 1,190) was then tested for association, adjusting for age, sex, site of recruitment, and admixture estimates (stage 2). In stage 3, additional SNPs were genotyped in four genic regions showing evidence of association in stage 2. Several SNPs were associated in the GWAS (P < 1 × 10?5) and were confirmed to be significantly associated in the entire Hispanic cohort (P < 0.01), including: rs7543757 for VAT, rs4754373 and rs11212913 for SAT, and rs4541696 and rs4134351 for VSR. Numerous SNPs were associated with multiple adiposity phenotypes. Targeted analysis of four genes whose SNPs were significant in stage 2 suggests candidate genes for influencing the distribution (RGS6) and amount of adiposity (NGEF). Several candidate loci, including RGS6 and NGEF, are associated with CT‐derived adipose fat measures in Hispanic Americans in a three‐stage genetic association study. |
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