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PMID: 20170901 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Systems genetics analysis of gene-by-environment interactions in human cells.

American journal of human genetics ·Vol. 86 ·No. 3 ·2010-03-12 ·Pages 399-410

Romanoski CE, Lee S, Kim MJ, Ingram-Drake L, Plaisier CL, Yordanova R, Tilford C, Guan B, He A, Gargalovic PS, Kirchgessner TG, Berliner JA, Lusis AJ

Abstract

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.

MeSH Terms
Cell Line Endothelial Cells/drug effects,metabolism Environment Female Gene Expression Regulation/drug effects Genetic Variation Genome-Wide Association Study Humans Male Models, Genetic Oligonucleotide Array Sequence Analysis Phosphatidylcholines/pharmacology Polymorphism, Single Nucleotide Quantitative Trait Loci RNA, Small Interfering/genetics Systems Biology Transcription, Genetic
Chemicals
Phosphatidylcholines RNA, Small Interfering oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Romanoski Casey E
Department of Human Genetics, University of California, Los Angeles, CA, 90095, USA. [email protected]
Lee Sangderk
Kim Michelle J
Ingram-Drake Leslie
Plaisier Christopher L
Yordanova Roumyana
Tilford Charles
Guan Bo
He Aiqing
Gargalovic Peter S
Kirchgessner Todd G
Berliner Judith A
Lusis Aldons J
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Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
1537-6605
DOI
10.1016/j.ajhg.2010.02.002
Email
[email protected]
Published
2010-03-12
Epub
2010-00-18
Pages
399-410
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC2833388
Subset
IM
Grants
NHLBI NIH HHS · HL069766 · United States
NHGRI NIH HHS · T32 HG002536 · United States
NHLBI NIH HHS · P01-HL030568 · United States
NHLBI NIH HHS · P01 HL030568 · United States
NHLBI NIH HHS · T32 HL069766 · United States
Databases
GEO
GSE20060
External Links
PubMed source DOI: 10.1016/j.ajhg.2010.02.002 PMC Full Text View journal details
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