A genome-wide search for gene-by-obesity interaction loci of dyslipidemia in Koreans shows diverse genetic risk alleles [Patient-Oriented and Epidemiological Research]

Dyslipidemia is a well-established risk factor for CVD. Studies suggest that similar fat accumulation in a given population might result in different levels of dyslipidemia risk among individuals; for example, despite similar or leaner body composition compared with Caucasians, Asians of Korean descent experience a higher prevalence of dyslipidemia. These variations imply a possible role of gene-obesity interactions on lipid profiles. Genome-wide association studies have identified more than 500 loci regulating plasma lipids, but the interaction structure between genes and obesity traits remains unclear. We hypothesized that some loci modify the effects of obesity on dyslipidemia risk and analyzed extensive gene-environment interactions (GxEs) at genome-wide levels to search for replicated gene-obesity interactive SNPs. In four Korean cohorts (n = 18,025), we identified and replicated 20 gene-obesity interactions, including novel variants (SCN1A and SLC12A8) and known lipid-associated variants (APOA5, BUD13, ZNF259, and HMGCR). When we estimated the additional heritability of dyslipidemia by considering GxEs, the gain was substantial for triglycerides (TGs) but mild for LDL cholesterol (LDL-C) and total cholesterol (Total-C); the interaction explained up to 18.7% of TG, 2.4% of LDL-C, and 1.9% of Total-C heritability associated with waist-hip ratio. Our findings suggest that some individuals are prone to develop abnormal lipid profiles, particularly with regard to TGs, even w...
Source: The Journal of Lipid Research - Category: Lipidology Authors: Tags: Patient-Oriented and Epidemiological Research Source Type: research