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