Association of LPL SNPs with lipid concentrations
We sequentially discarded 6 SNPs with MAF < 0.05, 2 SNPs with call rate < 95%, and 1 SNP with HWE p-value < 0.002, leaving 19 SNPs for the association study at stage 1. Our results show that SNPs located in the LPL gene, including the 3' flanking region, were strongly associated with HDLC and TG levels. The linear regression, adjusted for age, gender, and BMI, using combined data from the two study stages, revealed that 15 SNPs were associated with HDLC and TG levels (Table 2). The strongest associations were between rs10503669 and both HDLC (combined p = 3.6 × 10-22; 2.2-mg/dL increase per minor T allele) and TG (combined p = 3 × 10-15; 13.6-mg/dL decrease per minor T allele) in additive models. However, no strong association was detected between the SNP and either LDLC or TCHL levels (Supplementary Fig. 1).
For LPL SNPs, we tested 2 intronic SNPs and 2 SNPs located in the 3' untranslated region (UTR) from stage 1. Of these, two SNPs in the 3' UTR (rs11570892 and rs3200218) were not significantly associated with any lipid concentration (Supplementary Table 1). Two intronic SNPs, rs263 and rs271, were significantly associated to higher HDLC levels (p = 1.2 × 10-10 and p = 2.5 × 10-11; 1.2- and 1.3-mg/dL increase per minor A and T allele, respectively) and lower TG levels (p = 1.7 × 10-6 and p = 7.2 × 10-7; 8.8- and 9-mg/dL decrease per minor A and T allele, respectively) (Table 2). In stage 2, 7 intronic SNPs and 2 SNPs that were located in the 3' UTR were tested. It was found that rs263 and rs271 were also strongly associated with increased HDLC (p = 5.5 × 10-6 and p = 5.1 × 10-6, respectively; both showed a 1.5-mg/dL increase per minor A and T allele) (Table 2) and decreased TG levels (p = 3.3 × 10-3 and p = 2.2 × 10-3; 8.6- and 8.7-mg/dL decrease per minor A and T allele, respectively). Additionally, 4 intronic SNPs (rs253, rs326, rs327, and rs12679834) were significantly associated with increased HDLC (p = 4.2 × 10-3, p = 1.5 × 10-9, p = 1.6 × 10-9 and p = 3.1 × 10-14; increase of 0.8, 2.1, 2.1, and 3.3 mg/dL per minor allele, respectively) and decreased TG levels (p = 3.6 × 10-3, p = 9.1 × 10-7, p = 5.9 × 10-7 and p = 1.3 × 10-6; increase of 7.4, 12.2, 12.3, and 13.7 mg/dL per minor allele, respectively) (Supplementary Table 2). The analysis using combined data from the two stages showed that rs263 and rs271 were also significantly associated with HDLC (p = 1.7 × 10-11 and p = 5.7 × 10-12, respectively; increase in both cases of 1.2 mg/dL per minor A and T allele) and TG levels (p = 6.8 × 10-7 and p = 2.7 × 10-7; decrease of 8.1, 8.3 mg/dL per minor A and T allele, respectively) (Table 2).