Adiposity amplifies the genetic risk of fatty liver disease conferred by multiple loci

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

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.

In: Nature Genetics, Vol. 49, No. 6, 06.2017, p. 842-847.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Stender, S, Kozlitina, J, Nordestgaard, BG, Tybjærg-Hansen, A, Hobbs, HH & Cohen, JC 2017, 'Adiposity amplifies the genetic risk of fatty liver disease conferred by multiple loci', Nature Genetics, vol. 49, no. 6, pp. 842-847. https://doi.org/10.1038/ng.3855

APA

Stender, S., Kozlitina, J., Nordestgaard, B. G., Tybjærg-Hansen, A., Hobbs, H. H., & Cohen, J. C. (2017). Adiposity amplifies the genetic risk of fatty liver disease conferred by multiple loci. Nature Genetics, 49(6), 842-847. https://doi.org/10.1038/ng.3855

Vancouver

Stender S, Kozlitina J, Nordestgaard BG, Tybjærg-Hansen A, Hobbs HH, Cohen JC. Adiposity amplifies the genetic risk of fatty liver disease conferred by multiple loci. Nature Genetics. 2017 Jun;49(6):842-847. https://doi.org/10.1038/ng.3855

Author

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. In: Nature Genetics. 2017 ; Vol. 49, No. 6. pp. 842-847.

Bibtex

@article{4148a984ec9c45cbac257161a60e41b9,
title = "Adiposity amplifies the genetic risk of fatty liver disease conferred by multiple loci",
abstract = "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 (encoding PNPLA3 p.I148M, TM6SF2 p.E167K, and GCKR p.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 interaction between adiposity and sequence variants influencing other adiposity-associated traits. These results indicate that adiposity augments genetic risk of NAFLD at multiple loci that confer susceptibility to hepatic steatosis through diverse metabolic mechanisms.",
author = "Stefan Stender and Julia Kozlitina and Nordestgaard, {B{\o}rge G.} and Anne Tybj{\ae}rg-Hansen and Hobbs, {Helen H.} and Cohen, {Jonathan C.}",
year = "2017",
month = jun,
doi = "10.1038/ng.3855",
language = "English",
volume = "49",
pages = "842--847",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "nature publishing group",
number = "6",

}

RIS

TY - JOUR

T1 - Adiposity amplifies the genetic risk of fatty liver disease conferred by multiple loci

AU - Stender, Stefan

AU - Kozlitina, Julia

AU - Nordestgaard, Børge G.

AU - Tybjærg-Hansen, Anne

AU - Hobbs, Helen H.

AU - Cohen, Jonathan C.

PY - 2017/6

Y1 - 2017/6

N2 - 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 (encoding PNPLA3 p.I148M, TM6SF2 p.E167K, and GCKR p.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 interaction between adiposity and sequence variants influencing other adiposity-associated traits. These results indicate that adiposity augments genetic risk of NAFLD at multiple loci that confer susceptibility to hepatic steatosis through diverse metabolic mechanisms.

AB - 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 (encoding PNPLA3 p.I148M, TM6SF2 p.E167K, and GCKR p.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 interaction between adiposity and sequence variants influencing other adiposity-associated traits. These results indicate that adiposity augments genetic risk of NAFLD at multiple loci that confer susceptibility to hepatic steatosis through diverse metabolic mechanisms.

U2 - 10.1038/ng.3855

DO - 10.1038/ng.3855

M3 - Journal article

C2 - 28436986

AN - SCOPUS:85018256652

VL - 49

SP - 842

EP - 847

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 6

ER -

ID: 188713594