TY - JOUR
T1 - Epistasis between SNPs in genes involved in lipoprotein metabolism influences high- and low-density lipoprotein cholesterol levels
AU - Kim, Sunshin
AU - Shin, Chol
AU - Cho, Nam H.
AU - Koh, In Song
AU - Ko, Jeong Jae
AU - Kwack, Kyu Bum
N1 - Publisher Copyright:
© 2014, The Genetics Society of Korea and Springer-Science and Media.
Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.
PY - 2014/11/27
Y1 - 2014/11/27
N2 - Although genome-wide association (GWA) studies have provided valuable insights into the genetic architecture of human disease, they have elucidated relatively little of the heritability of complex traits. A significant part of the missing heritability might be explained by rare combinations of common SNPs. We hypothesized that epistasis among 15 genes (148 SNPs) involved in lipoprotein metabolism would influence HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) levels. Using SNPwinter software with the various epistatic models, we identified 58 association signals with HDL-C levels for SNPs in eleven genes and 118 associations with LDL-C for SNPs in fourteen genes. These associations were discovered in the urban Ansan cohort (n = 4,102) and replicated in a rural cohort (n = 3,434), the Ansung. We found replicated associations with new genes (SOAT1, APOB, HMGCR, and FDFT1 for HDL-C, and SOAT1, FDFT1, LPL, SQLE, ABCA1, LRP1, SCARB1, and PLTP for LDL-C), 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 by GWA studies, through investigating pairwise interactions between candidate genes of biological and clinical importance. Interestingly, we found that some genes were more likely to be involved in epistatic interactions (ABCA1 and LIPC for HDL-C, and ABCA1, SCARB1, and LIPC for LDL-C).
AB - Although genome-wide association (GWA) studies have provided valuable insights into the genetic architecture of human disease, they have elucidated relatively little of the heritability of complex traits. A significant part of the missing heritability might be explained by rare combinations of common SNPs. We hypothesized that epistasis among 15 genes (148 SNPs) involved in lipoprotein metabolism would influence HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) levels. Using SNPwinter software with the various epistatic models, we identified 58 association signals with HDL-C levels for SNPs in eleven genes and 118 associations with LDL-C for SNPs in fourteen genes. These associations were discovered in the urban Ansan cohort (n = 4,102) and replicated in a rural cohort (n = 3,434), the Ansung. We found replicated associations with new genes (SOAT1, APOB, HMGCR, and FDFT1 for HDL-C, and SOAT1, FDFT1, LPL, SQLE, ABCA1, LRP1, SCARB1, and PLTP for LDL-C), 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 by GWA studies, through investigating pairwise interactions between candidate genes of biological and clinical importance. Interestingly, we found that some genes were more likely to be involved in epistatic interactions (ABCA1 and LIPC for HDL-C, and ABCA1, SCARB1, and LIPC for LDL-C).
KW - Epistatic interaction
KW - Lipoprotein
KW - Metabolism
KW - SNPwinter
KW - Single nucleotide polymorphism (SNP)
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U2 - 10.1007/s13258-014-0216-7
DO - 10.1007/s13258-014-0216-7
M3 - Article
AN - SCOPUS:84912010720
SN - 1976-9571
VL - 36
SP - 809
EP - 817
JO - Genes and Genomics
JF - Genes and Genomics
IS - 6
ER -