Adiposity Amplifies the Genetic Risk of Fatty Liver Disease Conferred by Multiple Loci

Complex traits arise from the interplay between genetic and environmental factors. The actions of these factors usually appear to be additive, and few compelling examples of gene-environment synergy have been documented. Here we show that adiposity significantly amplifies the effect of three sequenc...

Descripción completa

Detalles Bibliográficos
Autores principales: Stender, Stefan, Kozlitina, Julia, Nordestgaard, Børge G., Tybjærg-Hansen, Anne, Hobbs, Helen H., Cohen, Jonathan C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2017
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562020/
https://www.ncbi.nlm.nih.gov/pubmed/28436986
http://dx.doi.org/10.1038/ng.3855
_version_ 1783257907367772160
author Stender, Stefan
Kozlitina, Julia
Nordestgaard, Børge G.
Tybjærg-Hansen, Anne
Hobbs, Helen H.
Cohen, Jonathan C.
author_facet Stender, Stefan
Kozlitina, Julia
Nordestgaard, Børge G.
Tybjærg-Hansen, Anne
Hobbs, Helen H.
Cohen, Jonathan C.
author_sort Stender, Stefan
collection PubMed
description Complex traits arise from the interplay between genetic and environmental factors. The actions of these factors usually appear to be additive, and few compelling examples of gene-environment synergy have been documented. Here we show that adiposity significantly amplifies the effect of three sequence variants (PNPLA3-I148M, TM6SF2-E167K and GCKR-P446L) associated with nonalcoholic fatty liver disease (NAFLD). Synergy between adiposity and genotype promoted the full spectrum of NAFLD, from steatosis to hepatic inflammation to cirrhosis. We found no evidence of strong interactions between adiposity and sequence variants influencing other adiposity-associated traits. These results indicate that adiposity may augment genetic risk of NAFLD at multiple loci through at least three different metabolic mechanisms.
format Online
Article
Text
id pubmed-5562020
institution National Center for Biotechnology Information
language English
publishDate 2017
record_format MEDLINE/PubMed
spelling pubmed-55620202017-10-24 Adiposity Amplifies the Genetic Risk of Fatty Liver Disease Conferred by Multiple Loci Stender, Stefan Kozlitina, Julia Nordestgaard, Børge G. Tybjærg-Hansen, Anne Hobbs, Helen H. Cohen, Jonathan C. Nat Genet Article Complex traits arise from the interplay between genetic and environmental factors. The actions of these factors usually appear to be additive, and few compelling examples of gene-environment synergy have been documented. Here we show that adiposity significantly amplifies the effect of three sequence variants (PNPLA3-I148M, TM6SF2-E167K and GCKR-P446L) associated with nonalcoholic fatty liver disease (NAFLD). Synergy between adiposity and genotype promoted the full spectrum of NAFLD, from steatosis to hepatic inflammation to cirrhosis. We found no evidence of strong interactions between adiposity and sequence variants influencing other adiposity-associated traits. These results indicate that adiposity may augment genetic risk of NAFLD at multiple loci through at least three different metabolic mechanisms. 2017-04-24 2017-06 /pmc/articles/PMC5562020/ /pubmed/28436986 http://dx.doi.org/10.1038/ng.3855 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Stender, Stefan
Kozlitina, Julia
Nordestgaard, Børge G.
Tybjærg-Hansen, Anne
Hobbs, Helen H.
Cohen, Jonathan C.
Adiposity Amplifies the Genetic Risk of Fatty Liver Disease Conferred by Multiple Loci
title Adiposity Amplifies the Genetic Risk of Fatty Liver Disease Conferred by Multiple Loci
title_full Adiposity Amplifies the Genetic Risk of Fatty Liver Disease Conferred by Multiple Loci
title_fullStr Adiposity Amplifies the Genetic Risk of Fatty Liver Disease Conferred by Multiple Loci
title_full_unstemmed Adiposity Amplifies the Genetic Risk of Fatty Liver Disease Conferred by Multiple Loci
title_short Adiposity Amplifies the Genetic Risk of Fatty Liver Disease Conferred by Multiple Loci
title_sort adiposity amplifies the genetic risk of fatty liver disease conferred by multiple loci
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562020/
https://www.ncbi.nlm.nih.gov/pubmed/28436986
http://dx.doi.org/10.1038/ng.3855
work_keys_str_mv AT stenderstefan adiposityamplifiesthegeneticriskoffattyliverdiseaseconferredbymultipleloci
AT kozlitinajulia adiposityamplifiesthegeneticriskoffattyliverdiseaseconferredbymultipleloci
AT nordestgaardbørgeg adiposityamplifiesthegeneticriskoffattyliverdiseaseconferredbymultipleloci
AT tybjærghansenanne adiposityamplifiesthegeneticriskoffattyliverdiseaseconferredbymultipleloci
AT hobbshelenh adiposityamplifiesthegeneticriskoffattyliverdiseaseconferredbymultipleloci
AT cohenjonathanc adiposityamplifiesthegeneticriskoffattyliverdiseaseconferredbymultipleloci

Ejemplares similares