Systems genetics analysis of gene-by-environment interactions in human cells
Open accessAbstract
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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More than 30% of gene transcripts are substantially influenced by eQTLs.
“Studies have revealed that over 30% of gene transcripts are substantially influenced by eQTLs (Romanoski et al., 2010).”
From Integrative Analysis of Multi-omics Data for Discovery and Functional Studies of Complex Human Diseases (2016) · cites this paper as Romanoski et al., 2010
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References 62 · Cited by 111
- Authors
- Romanoski, C. E., Lee, S., Kim, M. J., Ingram-Drake, L., Plaisier, C. L., Yordanova, R., Tilford, C., Guan, B., He, A., Gargalovic, P. S., Kirchgessner, T. G., Berliner, J. A., & Lusis, A. J.
- Affiliations
- University of California, Los Angeles (US)
- Institute for Systems Biology (US)
- Bristol-Myers Squibb (United States) (US)
- Corresponding author
- Romanoski, Casey E.
- Lusis, Aldons J.
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2010-03
- Volume
- 86
- Issue
- 3
- Pages
- 399-410
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC2833388
- OpenAlex
- W2083380010
- Cited by
- 111
- References
- 62
- Citations by year
- 2025: 7 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 2 · 2020: 10 · 2019: 6 · 2018: 7 · 2017: 7 · 2016: 9 · 2015: 6 · 2014: 12 · 2013: 10 · 2012: 14
- FWCI
- 6.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- Bristol-Myers Squibb
- National Institutes of Health (HL030568)
- National Heart, Lung, and Blood Institute (P01HL030568, T32HL069766, HL069766)
- National Human Genome Research Institute (T32HG002536)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- gene-environment interaction, endothelial cells, oxidized phospholipids, mRNA levels, cardiovascular disease, distal regulatory elements, siRNA knockdown, complex human traits
- MeSH terms
- Cell Line, Environment, Female, Gene Expression Regulation, Humans, Male, Models, Genetic, Phosphatidylcholines, Transcription, Genetic, Genetic Variation, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, RNA, Small Interfering, Quantitative Trait Loci, Endothelial Cells, Systems Biology, Genome-Wide Association Study
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