Mapping adipose and muscle tissue expression quantitative trait loci in African Americans to identify genes for type 2 diabetes and obesity

Satria P. Sajuthi, Neeraj K. Sharma, Jeff W. Chou, Nicholette D. Palmer, David R. McWilliams, John Beal, Mary E. Comeau, Lijun Ma, Jorge Calles-Escandon, Jamehl Demons, Samantha Rogers, Kristina Cherry, Lata Menon, Ethel Kouba, Donna Davis, Marcie Burris, Sara J. Byerly, Maggie C Y Ng, Nisa Maruthur, Sanjay R. PatelLawrence F. Bielak, Leslie A. Lange, Xiuqing Guo, Michèle M. Sale, Kei Hang K Chan, Keri L. Monda, Gary K. Chen, Kira Taylor, Cameron Palmer, Todd L. Edwards, Kari E. North, Christopher A. Haiman, Donald W. Bowden, Barry I. Freedman, Carl D. Langefeld, Swapan K. Das

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1-12
Number of pages12
JournalHuman Genetics
DOIs
Publication statusAccepted/In press - May 19 2016

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ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Sajuthi, S. P., Sharma, N. K., Chou, J. W., Palmer, N. D., McWilliams, D. R., Beal, J., ... Das, S. K. (Accepted/In press). Mapping adipose and muscle tissue expression quantitative trait loci in African Americans to identify genes for type 2 diabetes and obesity. Human Genetics, 1-12. https://doi.org/10.1007/s00439-016-1680-8