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Reverse gene-environment interaction approach to identify variants influencing body-mass index in humans.
Garske, Kristina M; Pan, David Z; Miao, Zong; Bhagat, Yash V; Comenho, Caroline; Robles, Christopher R; Benhammou, Jihane N; Alvarez, Marcus; Ko, Arthur; Ye, Chun Jimmie; Pisegna, Joseph R; Mohlke, Karen L; Sinsheimer, Janet S; Laakso, Markku; Pajukanta, Päivi.
Afiliação
  • Garske KM; Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA, 90095.
  • Pan DZ; Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA, 90095.
  • Miao Z; Bioinformatics Interdepartmental Program, UCLA, Los Angeles, CA, USA, 90095.
  • Bhagat YV; Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA, 90095.
  • Comenho C; Bioinformatics Interdepartmental Program, UCLA, Los Angeles, CA, USA, 90095.
  • Robles CR; Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA, 90095.
  • Benhammou JN; Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA, 90095.
  • Alvarez M; Department of Computer Science, UCLA, Los Angeles, CA, USA, 90095.
  • Ko A; Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA, 90095.
  • Ye CJ; Vache and Tamar Manoukian Division of Digestive Diseases, UCLA, Los Angeles, CA, USA, 90095.
  • Pisegna JR; Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA, 90095.
  • Mohlke KL; Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA, 90095.
  • Sinsheimer JS; Institute for Human Genetics, Department of Epidemiology and Biostatistics, Department of Bioengineering and Therapeutic Sciences, UCSF, San Francisco, CA, USA, 94143.
  • Laakso M; Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA, 90095.
  • Pajukanta P; Vache and Tamar Manoukian Division of Digestive Diseases, UCLA, Los Angeles, CA, USA, 90095.
Nat Metab ; 1(6): 630-642, 2019 06.
Article em En | MEDLINE | ID: mdl-31538139
ABSTRACT
Identifying gene-environment interactions (GxEs) contributing to human cardiometabolic disorders is challenging. Here we apply a reverse GxE candidate search by deriving candidate variants from promoter-enhancer interactions that respond to dietary fatty acid challenge through altered chromatin accessibility in human primary adipocytes. We then test all variants residing in the lipid-responsive open chromatin sites within adipocyte promoter-enhancer contacts for interaction effects between the genotype and dietary saturated fat intake on body mass index (BMI) in the UK Biobank. We discover 14 novel GxE variants in 12 lipid-responsive promoters, including well-known lipid genes (LIPE, CARM1, and PLIN2) and novel genes, such as LDB3, for which we provide further functional and integrative genomics evidence. We further identify 24 GxE variants in enhancers, totaling 38 new GxE variants for BMI in the UK Biobank, demonstrating that molecular genomics data produced in physiologically relevant contexts can discover new functional GxE mechanisms in humans.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Índice de Massa Corporal / Interação Gene-Ambiente Limite: Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Índice de Massa Corporal / Interação Gene-Ambiente Limite: Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article