ArticlePloS one2014
Analysis of multiple association studies provides evidence of an expression QTL hub in gene-gene interaction network affecting HDL cholesterol levels.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 15 citations in OpenAlex.
- Multivariate Genome-Wide Association Analysis Identifies Genetic Susceptibility Loci for Metabolic Syndrome in the Korean Genome and Epidemiology Study.International journal of molecular sciences · 2026Article
- MR-GGI: accurate inference of gene-gene interactions using Mendelian randomization.BMC bioinformatics · 2024Article
- Pleiotropic association of LIPC variants with lipid and urinary 8-hydroxy deoxyguanosine levels in a Taiwanese population.Lipids in health and disease · 2019Article
- The intragenic mRNA-microRNA regulatory network during telogen-anagen hair follicle transition in the cashmere goat.Scientific reports · 2018Article
- HDL-cholesterol concentration in pregnant Chinese Han women of late second trimester associated with genetic variants inOncotarget · 2017Article
- Prioritizing tests of epistasis through hierarchical representation of genomic redundancies.Nucleic acids research · 2017Article
- Article
- Missing heritability of common diseases and treatments outside the protein-coding exome.Human genetics · 2014Review
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4 authors at 2 institutions in 1 country.
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Abstract
Epistasis has been suggested to underlie part of the missing heritability in genome-wide association studies. In this study, we first report an analysis of gene-gene interactions affecting HDL cholesterol (HDL-C) levels in a candidate gene study of 2,091 individuals with mixed dyslipidemia from a clinical trial. Two additional studies, the Atherosclerosis Risk in Communities study (ARIC; n = 9,713) and the Multi-Ethnic Study of Atherosclerosis (MESA; n = 2,685), were considered for replication. We identified a gene-gene interaction between rs1532085 and rs12980554 (P = 7.1 × 10(-7)) in their effect on HDL-C levels, which is significant after Bonferroni correction (P(c) = 0.017) for the number of SNP pairs tested. The interaction successfully replicated in the ARIC study (P = 7.0 × 10(-4); P(c) = 0.02). Rs1532085, an expression QTL (eQTL) of LIPC, is one of the two SNPs involved in another, well-replicated gene-gene interaction underlying HDL-C levels. To further investigate the role of this eQTL SNP in gene-gene interactions affecting HDL-C, we tested in the ARIC study for interaction between this SNP and any other SNP genome-wide. We found the eQTL to be involved in a few suggestive interactions, one of which significantly replicated in MESA. Importantly, these gene-gene interactions, involving only rs1532085, explain an additional 1.4% variation of HDL-C, on top of the 0.65% explained by rs1532085 alone. LIPC plays a key role in the lipid metabolism pathway and it, and rs1532085 in particular, has been associated with HDL-C and other lipid levels. Collectively, we discovered several novel gene-gene interactions, all involving an eQTL of LIPC, thus suggesting a hub role of LIPC in the gene-gene interaction network that regulates HDL-C levels, which in turn raises the hypothesis that LIPC's contribution is largely via interactions with other lipid metabolism related genes.
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