1. Mapping adipose and muscle tissue expression quantitative trait loci in African Americans to identify genes for type 2 diabetes and obesity.
- Author
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Sajuthi SP, Sharma NK, Chou JW, Palmer ND, McWilliams DR, Beal J, Comeau ME, Ma L, Calles-Escandon J, Demons J, Rogers S, Cherry K, Menon L, Kouba E, Davis D, Burris M, Byerly SJ, Ng MC, Maruthur NM, Patel SR, Bielak LF, Lange LA, Guo X, Sale MM, Chan KH, Monda KL, Chen GK, Taylor K, Palmer C, Edwards TL, North KE, Haiman CA, Bowden DW, Freedman BI, Langefeld CD, and Das SK
- Subjects
- Adipose Tissue pathology, Adolescent, Adult, Black or African American genetics, Chromosome Mapping, Diabetes Mellitus, Type 2 pathology, Female, Gene Expression Regulation, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Muscles pathology, Obesity pathology, Adipose Tissue metabolism, Diabetes Mellitus, Type 2 genetics, Muscles metabolism, Obesity genetics, Quantitative Trait Loci genetics
- Abstract
Relative to European Americans, type 2 diabetes (T2D) is more prevalent in African Americans (AAs). Genetic variation may modulate transcript abundance in insulin-responsive tissues and contribute to risk; yet, published studies identifying expression quantitative trait loci (eQTLs) in African ancestry populations are restricted to blood cells. This study aims to develop a map of genetically regulated transcripts expressed in tissues important for glucose homeostasis in AAs, critical for identifying the genetic etiology of T2D and related traits. Quantitative measures of adipose and muscle gene expression, and genotypic data were integrated in 260 non-diabetic AAs to identify expression regulatory variants. Their roles in genetic susceptibility to T2D, and related metabolic phenotypes, were evaluated by mining GWAS datasets. eQTL analysis identified 1971 and 2078 cis-eGenes in adipose and muscle, respectively. Cis-eQTLs for 885 transcripts including top cis-eGenes CHURC1, USMG5, and ERAP2 were identified in both tissues. 62.1 % of top cis-eSNPs were within ±50 kb of transcription start sites and cis-eGenes were enriched for mitochondrial transcripts. Mining GWAS databases revealed association of cis-eSNPs for more than 50 genes with T2D (e.g. PIK3C2A, RBMS1, UFSP1), gluco-metabolic phenotypes (e.g. INPP5E, SNX17, ERAP2, FN3KRP), and obesity (e.g. POMC, CPEB4). Integration of GWAS meta-analysis data from AA cohorts revealed the most significant association for cis-eSNPs of ATP5SL and MCCC1 genes, with T2D and BMI, respectively. This study developed the first comprehensive map of adipose and muscle tissue eQTLs in AAs (publically accessible at https://mdsetaa.phs.wakehealth.edu ) and identified genetically regulated transcripts for delineating genetic causes of T2D, and related metabolic phenotypes.
- Published
- 2016
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