Results
The clinical characteristics and statistics of the variables for each study sample are described in Table 1. Our previous large-scale GWAS identified 9 novel and 24 known genetic loci influencing metabolic traits in East Asians [9]. In an attempt to determine whether well-established lipid-related variants contribute to significant and reproducible genetic factors for susceptibility to blood lipid concentrations in a childhood obesity study, we first examined the associations between individual genetic variants and lipid-related phenotypes using linear regression analysis.
Of these 16 SNPs for blood lipid traits, rs10503669 in LPL (genotyped SNP in a childhood obesity study) was significantly associated with TG and HDL-C, respectively. In addition, rs16940212 in LIPC (linkage disequilibrium-based proxy SNP) was associated with HDL-C (Table 2). The direction of these associations was consistent with our previous GWAS [9].
Having two loci (rs10503669 at LPL and rs16940212 at LIPC) showing the strongest association with TG and HDL-C, we next investigated whether the cumulative allelic dosage of risk alleles contributes to the quantitative variation of lipoprotein concentrations in the KARE study using a method of calculating a GRS. We evaluated the joint effects of the best-associated SNPs at the two loci showing evidence of association with HDL-C (rs10503669 at LPL and rs16940212 at LIPC). We calculated a GRS, representing the sum of the risk alleles, and observed that increasing GRS was significantly associated with decreased HDL-C (effect size, -1.13 ± 0.07) compared to SNP combinations without two risk variants (Fig. 1). In addition, a positive correlation was observed between allelic dosage score and risk allele (rs10503669 at LPL) for high TG levels (effect size, 10.89 ± 0.84) (Fig. 2).