TY - JOUR
T1 - Systems Genetics Analysis of Gene-by-Environment Interactions in Human Cells
AU - Romanoski, Casey E.
AU - Lee, Sangderk
AU - Kim, Michelle J.
AU - Ingram-Drake, Leslie
AU - Plaisier, Christopher L.
AU - Yordanova, Roumyana
AU - Tilford, Charles
AU - Guan, Bo
AU - He, Aiqing
AU - Gargalovic, Peter S.
AU - Kirchgessner, Todd G.
AU - Berliner, Judith A.
AU - Lusis, Aldons J.
N1 - Funding Information:
This research was funded by NIH grant PO1-HL030568 (A.J.L. and J.A.B.), NIH training grant HL069766 (C.E.R.), an American Heart Association pre-doctoral fellowship (C.E.R.) and an American Heart Association postdoctoral fellowship (S.D.L.). We would like to thank the Atherosclerosis Research Unit (ARU) at UCLA for help collecting the HAECs and Calvin Pan for data management. R.Y., C.T., B.G., A.H., P.S.G., and T.G.K. are employees and shareholders of Bristol-Myers Squibb.
PY - 2010
Y1 - 2010
N2 - Gene by environment (GxE) interactions are clearly important in many human diseases, but they have proven to be difficult to study on a molecular level. We report genetic analysis of thousands of transcript abundance traits in human primary endothelial cell (EC) lines in response to proinflammatory oxidized phospholipids implicated in cardiovascular disease. Of the 59 most regulated transcripts, approximately one-third showed evidence of GxE interactions. The interactions resulted primarily from effects of distal-, trans-acting loci, but a striking example of a local-GxE interaction was also observed for FGD6. Some of the distal interactions were validated by siRNA knockdown experiments, including a locus involved in the regulation of multiple transcripts involved in the ER stress pathway. Our findings add to the understanding of the overall architecture of complex human traits and are consistent with the possibility that GxE interactions are responsible, in part, for the failure of association studies to more fully explain common disease variation.
AB - Gene by environment (GxE) interactions are clearly important in many human diseases, but they have proven to be difficult to study on a molecular level. We report genetic analysis of thousands of transcript abundance traits in human primary endothelial cell (EC) lines in response to proinflammatory oxidized phospholipids implicated in cardiovascular disease. Of the 59 most regulated transcripts, approximately one-third showed evidence of GxE interactions. The interactions resulted primarily from effects of distal-, trans-acting loci, but a striking example of a local-GxE interaction was also observed for FGD6. Some of the distal interactions were validated by siRNA knockdown experiments, including a locus involved in the regulation of multiple transcripts involved in the ER stress pathway. Our findings add to the understanding of the overall architecture of complex human traits and are consistent with the possibility that GxE interactions are responsible, in part, for the failure of association studies to more fully explain common disease variation.
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U2 - 10.1016/j.ajhg.2010.02.002
DO - 10.1016/j.ajhg.2010.02.002
M3 - Article
C2 - 20170901
AN - SCOPUS:77649236340
SN - 0002-9297
VL - 86
SP - 399
EP - 410
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 3
ER -