Epistasis between SNPs in genes involved in lipoprotein metabolism influences high- and low-density lipoprotein cholesterol levels

다국어 초록 (Multilingual Abstract)

Although genome-wide association (GWA)studies have provided valuable insights into the geneticarchitecture of human disease, they have elucidated relativelylittle of the heritability of complex traits. A significantpart of the missing heritability might be explained byrare combinations of common SNPs. We hypothesized thatepistasis among 15 genes (148 SNPs) involved in lipoproteinmetabolism would influence HDL-cholesterol(HDL-C) and LDL-cholesterol (LDL-C) levels. UsingSNPwinter software with the various epistatic models, weidentified 58 association signals with HDL-C levels forSNPs in eleven genes and 118 associations with LDL-C forSNPs in fourteen genes. These associations were discoveredin the urban Ansan cohort (n = 4,102) and replicatedin a rural cohort (n = 3,434), the Ansung. We found replicatedassociations with new genes (SOAT1, APOB,HMGCR, and FDFT1 for HDL-C, and SOAT1, FDFT1,LPL, SQLE, ABCA1, LRP1, SCARB1, and PLTP for LDLC),in addition to those (CETP, LIPC, LPL, ABCA1, PLTP,SCARB1, and LRP1 for HDL-C, and CETP, LIPC, LDLR,APOB, CYP7A1, and HMGCR for LDL-C) identified byGWA studies, through investigating pairwise interactionsbetween candidate genes of biological and clinical importance.
Interestingly, we found that some genes were morelikely to be involved in epistatic interactions (ABCA1 andLIPC for HDL-C, and ABCA1, SCARB1, and LIPC forLDL-C).

참고문헌 (Reference)

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