A genome-wide search for gene-by-obesity interaction loci of dyslipidemia in Koreans shows diverse genetic risk alleles
Autor: | Moonil Kang, Joohon Sung |
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Rok vydání: | 2019 |
Předmět: |
Adult
Male 0301 basic medicine obesity Population Single-nucleotide polymorphism QD415-436 030204 cardiovascular system & hematology Biology Biochemistry Cohort Studies lipids 03 medical and health sciences 0302 clinical medicine Endocrinology Missing heritability problem Republic of Korea medicine Humans Genetic Predisposition to Disease Allele Risk factor dyslipidemias education triglycerides Alleles Aged Genetic association Genetics education.field_of_study Genomics Cell Biology Middle Aged Heritability medicine.disease 030104 developmental biology Genetic Loci high density lipoprotein Female lipids (amino acids peptides and proteins) Patient-Oriented and Epidemiological Research low density lipoprotein Dyslipidemia |
Zdroj: | Journal of Lipid Research, Vol 60, Iss 12, Pp 2090-2101 (2019) J Lipid Res |
ISSN: | 0022-2275 |
Popis: | 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 (G×Es) 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 G×Es, 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 with slight increases in obesity indices; ethnic diversities in the risk alleles might partly explain the differential dyslipidemia risk between populations. Research about these interacting variables may facilitate knowledge-based approaches to personalize health guidelines according to individual genetic profiles. |
Databáze: | OpenAIRE |
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