Table 1. Variants independently associated with blood lipids at exome-wide significance (P<2.69 × 10−7).
| Locus | SNPs | Annotation | Position | Alleles* | Trait(s) |
PUUMA-MI (N=7,452) |
HKU-TRS (N=5,233) |
Combined (N=12,685) |
||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EAF (%)† | Effect (s.e.)‡ | P | EAF (%) | Effect (s.e.) | P | EAF (%) | Effect (s.e.) | P | ||||||
| Novel associations at newly identified loci | ||||||||||||||
| PKD1L3 | rs7185272 | p.Thr429Ser | 16:72013797 | G/C | LDL-C | 76.0 | 0.07 (0.02) | 6.4 × 10−4 | 71.1 | 0.09 (0.02) | 1.4 × 10−5 | 74.0 | 0.08 (0.01) | 5.4 × 10−8 |
| TC | 0.06 (0.02) | 1.5 × 10−3 | 0.09 (0.02) | 2.7 × 10−5 | 0.07 (0.01) | 2.5 × 10−7 | ||||||||
| PNPLA3 | rs738409 | p.Ile148Met | 22:44324727 | C/G | TG | 36.5 | −0.06 (0.02) | 7.3 × 10−4 | 37.1 | −0.09 (0.02) | 6.9 × 10−6 | 36.7 | −0.07 (0.01) | 4.4 × 10−8 |
| Asian-specific associations at known loci | ||||||||||||||
| PCSK9 | rs151193009 | p.Arg93Cys | 1:55509585 | C/T | LDL-C | 1.7 | −0.65 (0.06) | 3.2 × 10−25 | 0.8 | −0.61 (0.11) | 3.7 × 10−8 | 1.3 | −0.64 (0.05) | 7.9 × 10−32 |
| TC | −0.58 (0.06) | 2.0 × 10−20 | −0.50 (0.11) | 4.0 × 10−6 | −0.56 (0.05) | 5.1 × 10−25 | ||||||||
| CETP | rs2303790 | p.Asp459Gly | 16:5701729 | A/G | HDL-C | 2.3 | 0.36 (0.05) | 3.3 × 10−11 | 3.2 | 0.53 (0.06) | 1.5 × 10−20 | 2.7 | 0.44 (0.04) | 3.2 × 10−29 |
| LDLR | rs200990725 | p.Arg257Trp | 19:11217315 | C/T | LDL-C | 0.03 | 1.43 (0.45) | 1.5 × 10−3 | 0.3 | 0.83 (0.18) | 2.6 × 10−6 | 0.1 | 0.91 (0.17) | 3.0 × 10−8 |
| Other independent associations at known loci | ||||||||||||||
| APOB | rs13306194 | p.Arg532Trp | 2:21252534 | G/A | LDL-C | 11.9 | −0.13 (0.03) | 7.5 × 10−8 | 14.2 | −0.13 (0.03) | 3.6 × 10−6 | 12.8 | −0.13 (0.02) | 1.2 × 10−12 |
| TC | −0.12 (0.03) | 1.0 × 10−8 | −0.14 (0.03) | 1.2 × 10−6 | −0.13 (0.02) | 6.0 × 10−12 | ||||||||
| APOA5§ | rs10466588 | Intergenic | 11:116610249 | A/G | TG | 14.2 | 0.08 (0.02) | 4.4 × 10−4 | 10.3 | 0.07 (0.03) | 0.036 | 12.6 | 0.08 (0.02) | 4.7 × 10−5 |
| HDL-C | −0.09 (0.02) | 1.7 × 10−4 | −0.03 (0.03) | 0.321 | −0.07 (0.02) | 2.9 × 10−4 | ||||||||
| APOA5 | rs2075291 | p.Gly185Cys | 11:116661392 | C/A | HDL-C | 6.0 | −0.32 (0.03) | 8.1 × 10−21 | 6.1 | −0.27 (0.04) | 1.4 × 10−10 | 6.0 | −0.30 (0.03) | 1.2 × 10−29 |
| DOCK6 | rs737337 | p.Thr712Thr | 19:11347493 | T/C | TC | 29.2 | −0.10 (0.02) | 5.5 × 10−8 | 24.6 | −0.07 (0.02) | 2.3 × 10−3 | 27.3 | −0.09 (0.01) | 7.5 × 10−10 |
| APOE | rs445925 | Intergenic | 19:45415640 | G/A | TC | −0.26 (0.03) | 6.0 × 10−18 | −0.20 (0.03) | 4.8 × 10−10 | −0.23 (0.02) | 4.1 × 10−26 | |||
| APOE | rs769449 | Intronic | 19:45410002 | G/A | HDL-C | 8.5 | −0.18 (0.03) | 5.2 × 10−10 | 7.6 | −0.08 (0.04) | 0.026 | 8.1 | −0.14 (0.02) | 3.8 × 10−10 |
EAF, Effect allele frequency; HDL-C, high-density lipoprotein cholesterol; HKU-TRS, Hong Kong Theme-based Research Scheme; LDL-C, low-density lipoprotein cholesterol; PUUMA-MI, Peking University Health Science Center and the University of Michigan Medical School study of Myocardial Infarction; SNP, single nucleotide polymorphism; TC, total cholesterol; TG, triglyceride.
For SNPs associated with more than one lipid traits, association results were listed first with primary trait, followed by secondary trait(s).
*Reference/alternative effect alleles with respect to human reference genome hg19.
†EAFs, in percentage, are shown for PUUMA-MI, HKU-TRS and the combined meta-analysis.
‡Effect sizes with respect to the effect allele are presented in s.d.
§SNP with significant association after conditioning on the known variant. For results of conditional analysis, see Supplementary Data 1.