Generalizability and applicability of results obtained from populations of European descent regarding the effect direction and size of HDL-C level-associated genetic variants to the Hungarian general and Roma populations
2019
Abstract Objectives Large-scale association studies that mainly involve European populations identified many genetic loci related to high-density lipoprotein cholesterol (HDL-C) levels, one of the most important indicators of the risk for cardiovascular diseases. The question with intense speculation of whether the effect estimates obtained from European populations for different HDL-C level-related SNPs are applicable to the Roma ethnicity, the largest minority group in Europe with a South Asian origin, was addressed in the present study. Design The associations between 21 SNPs (in the genes LIPC(G), CETP, GALNT2, HMGCP, ABCA1, KCTD10 and WWOX) and HDL-C levels were examined separately in adults of the Hungarian general (N = 1542) and Roma (N = 646) populations by linear regression. Individual effects (direction and size) of single SNPs on HDL-C levels were computed and compared between the study groups and with data published in the literature. Results Significant associations between SNPs and HDL-C levels were more frequently found in general subjects than in Roma subjects (11 SNPs in general vs. 4 SNPs in Roma). The CETP gene variants rs1532624, rs708272 and rs7499892 consistently showed significant associations with HDL-C levels across the study groups (p ˂ 0.05), indicating a possible causal variant(s) in this region. Although nominally significant differences in effect size were found for three SNPs (rs693 in gene APOB, rs9989419 in gene CETP, and rs2548861 in gene WWOX) by comparing the general and Roma populations, most of these SNPs did not have a significant effect on HDL-C levels. The β coefficients for SNPs in the Roma population were found to be identical both in direction and magnitude to the effect obtained previously in large-scale studies on European populations. Conclusions The effect of the vast majority of the SNPs on HDL-C levels could be replicated in the Hungarian general and Roma populations, which indicates that the effect size measurements obtained from the literature can be used for risk estimation for both populations.
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