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Mapping adipose and muscle tissue expression quantitative trait loci in African Americans to identify genes for type 2 diabetes and obesity.
Sajuthi, Satria P; Sharma, Neeraj K; Chou, Jeff W; Palmer, Nicholette D; McWilliams, David R; Beal, John; Comeau, Mary E; Ma, Lijun; Calles-Escandon, Jorge; Demons, Jamehl; Rogers, Samantha; Cherry, Kristina; Menon, Lata; Kouba, Ethel; Davis, Donna; Burris, Marcie; Byerly, Sara J; Ng, Maggie C Y; Maruthur, Nisa M; Patel, Sanjay R; Bielak, Lawrence F; Lange, Leslie A; Guo, Xiuqing; Sale, Michèle M; Chan, Kei Hang K; Monda, Keri L; Chen, Gary K; Taylor, Kira; Palmer, Cameron; Edwards, Todd L; North, Kari E; Haiman, Christopher A; Bowden, Donald W; Freedman, Barry I; Langefeld, Carl D; Das, Swapan K.
Afiliação
  • Sajuthi SP; Division of Public Health Sciences, Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
  • Sharma NK; Center for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
  • Chou JW; Center for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
  • Palmer ND; Department of Internal Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157, USA.
  • McWilliams DR; Division of Public Health Sciences, Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
  • Beal J; Center for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
  • Comeau ME; Center for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
  • Ma L; Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
  • Calles-Escandon J; Center for Diabetes Research and Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
  • Demons J; Division of Public Health Sciences, Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
  • Rogers S; Center for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
  • Cherry K; Division of Public Health Sciences, Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
  • Menon L; Center for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
  • Kouba E; Division of Public Health Sciences, Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
  • Davis D; Center for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
  • Burris M; Center for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
  • Byerly SJ; Department of Internal Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157, USA.
  • Ng MC; Department of Internal Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157, USA.
  • Maruthur NM; Division of Endocrinology, Metro Health System, and School of Medicine, Case Western Reserve University, Cleveland, OH, 44105, USA.
  • Patel SR; Department of Internal Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157, USA.
  • Bielak LF; Department of Internal Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157, USA.
  • Lange LA; Department of Internal Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157, USA.
  • Guo X; Department of Internal Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157, USA.
  • Sale MM; Department of Internal Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157, USA.
  • Chan KH; Department of Internal Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157, USA.
  • Monda KL; Clinical Research Unit, Biomedical Research Services and Administration, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
  • Chen GK; Clinical Research Unit, Biomedical Research Services and Administration, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
  • Taylor K; Center for Diabetes Research and Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
  • Palmer C; Division of General Internal Medicine, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
  • Edwards TL; Department of Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
  • North KE; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Haiman CA; Department of Genetics, University of North Carolina, Chapel Hill, NC, 27599, USA.
  • Bowden DW; Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
  • Freedman BI; Department of Public Health Sciences and Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, 22908, USA.
  • Langefeld CD; Laboratory of Molecular Epidemiology and Nutrition, Department of Epidemiology, Brown University, Providence, RI, 02912, USA.
  • Das SK; Center for Observational Research, Amgen, Inc, Thousand Oaks, CA, 91320, USA.
Hum Genet ; 135(8): 869-80, 2016 08.
Article em En | MEDLINE | ID: mdl-27193597
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tecido Adiposo / Locos de Características Quantitativas / Diabetes Mellitus Tipo 2 / Músculos / Obesidade Tipo de estudo: Prognostic_studies / Systematic_reviews Limite: Adolescent / Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Hum Genet Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tecido Adiposo / Locos de Características Quantitativas / Diabetes Mellitus Tipo 2 / Músculos / Obesidade Tipo de estudo: Prognostic_studies / Systematic_reviews Limite: Adolescent / Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Hum Genet Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Estados Unidos