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Cross-tissue and tissue-specific eQTLs: partitioning the heritability of a complex trait.
Torres, Jason M; Gamazon, Eric R; Parra, Esteban J; Below, Jennifer E; Valladares-Salgado, Adan; Wacher, Niels; Cruz, Miguel; Hanis, Craig L; Cox, Nancy J.
Afiliação
  • Torres JM; Committee on Molecular Metabolism and Nutrition, University of Chicago, Chicago, IL 60637, USA.
  • Gamazon ER; Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
  • Parra EJ; Department of Anthropology, University of Toronto at Mississauga, Mississauga, ON L5L 1C6, Canada.
  • Below JE; Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX 77225, USA.
  • Valladares-Salgado A; Unidades de Investigacion Medica en Bioquimica y Unidad de Epidemiologia Clinica, Hospital de Especialidades, Centro Medico Nacional "Siglo XXI," Instituto Mexicano del Seguro Social, Mexico City, CP 06720, Mexico.
  • Wacher N; Unidades de Investigacion Medica en Bioquimica y Unidad de Epidemiologia Clinica, Hospital de Especialidades, Centro Medico Nacional "Siglo XXI," Instituto Mexicano del Seguro Social, Mexico City, CP 06720, Mexico.
  • Cruz M; Unidades de Investigacion Medica en Bioquimica y Unidad de Epidemiologia Clinica, Hospital de Especialidades, Centro Medico Nacional "Siglo XXI," Instituto Mexicano del Seguro Social, Mexico City, CP 06720, Mexico.
  • Hanis CL; Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX 77225, USA.
  • Cox NJ; Department of Medicine, University of Chicago, Chicago, IL 60637, USA. Electronic address: ncox@bsd.uchicago.edu.
Am J Hum Genet ; 95(5): 521-34, 2014 Nov 06.
Article em En | MEDLINE | ID: mdl-25439722
Top signals from genome-wide association studies (GWASs) of type 2 diabetes (T2D) are enriched with expression quantitative trait loci (eQTLs) identified in skeletal muscle and adipose tissue. We therefore hypothesized that such eQTLs might account for a disproportionate share of the heritability estimated from all SNPs interrogated through GWASs. To test this hypothesis, we applied linear mixed models to the Wellcome Trust Case Control Consortium (WTCCC) T2D data set and to data sets representing Mexican Americans from Starr County, TX, and Mexicans from Mexico City. We estimated the proportion of phenotypic variance attributable to the additive effect of all variants interrogated in these GWASs, as well as a much smaller set of variants identified as eQTLs in human adipose tissue, skeletal muscle, and lymphoblastoid cell lines. The narrow-sense heritability explained by all interrogated SNPs in each of these data sets was substantially greater than the heritability accounted for by genome-wide-significant SNPs (∼10%); GWAS SNPs explained over 50% of phenotypic variance in the WTCCC, Starr County, and Mexico City data sets. The estimate of heritability attributable to cross-tissue eQTLs was greater in the WTCCC data set and among lean Hispanics, whereas adipose eQTLs significantly explained heritability among Hispanics with a body mass index ≥ 30. These results support an important role for regulatory variants in the genetic component of T2D susceptibility, particularly for eQTLs that elicit effects across insulin-responsive peripheral tissues.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fenótipo / Locos de Características Quantitativas / Diabetes Mellitus Tipo 2 Tipo de estudo: Prognostic_studies Limite: Humans País/Região como assunto: Mexico Idioma: En Revista: Am J Hum Genet Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fenótipo / Locos de Características Quantitativas / Diabetes Mellitus Tipo 2 Tipo de estudo: Prognostic_studies Limite: Humans País/Região como assunto: Mexico Idioma: En Revista: Am J Hum Genet Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos