Table 1.
Association of rare and low-frequency variants with blood lipids
| Non-HDL-C (mmol/L) n = 119,146 |
HDL-C (mmol/L) n = 119,514 |
Triglycerides (% change) n = 80,111 |
||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Gene | Variant | rsID | A1/A2 | A2 (%) | Effect (95% Cl) | P | Effect (95% Cl) | P | Effect (95% Cl) | P |
| PCSK9 | p.Arg46Leu | rs11591147 | G/T | 1.17 | −0.58 (−0.65, −0.51) |
1.2 × 10−64 | 0.031 (0.003, 0.058) |
0.028 | −1.7 (−4.7, 1.3) |
0.25 |
| ANGPTL3 a | Splice region | rs372257803 | T/C | 0.27 | −0.30 (−0.44, −0.17) |
1.4 × 10−5 | −0.053 (−0.108, 0.003) |
0.063 | −16.9 (−21.9, −11.6) |
5.7 × 10−9 |
| ANGPTL3 a | p.Asp290His | 1:62602317 | G/C | 0.49 | −0.38 (−0.48, −0.29) |
7.2 × 10−15 | −0.043 (−0.082, −0.003) |
0.033 | −20.9 (−24.4, −17.3) |
1.6 × 10−24 |
| APOB | p.His1923Arg | rs533617 | T/C | 4.52 | −0.21 (−0.24, −0.17) |
1.3 × 10−32 | 0.047 (0.033, 0.061) |
4.6 × 10−11 | −6.0 (−8.7, −3.1) |
4.7 × 10−5 |
| APOB a | p.Gly1829Glufs | 2:21011381 | TC/T | 0.007 | −3.28 (−4.24, −2.32) |
1.7 × 10−11 | 0.33 (−0.08, 0.73) |
0.12 | −65.3 (−77.7, −46.1) |
2.6 × 10−6 |
| APOB a | p.Leu1550Arg | 2:21012219 | A/C | 0.017 | −2.04 (−2.60, −1.48) |
7.8 × 10−13 | 0.34 (0.11, 0.57) |
0.004 | −35.0 (−49.1, −17.0) |
5.6 × 10−4 |
| APOB a | p.Gln725 | rs374473614 | G/A | 0.02 | −3.09 (−3.63, −2.55) |
3.2 × 10−29 | 0.31 (0.09, 0.53) |
5.9 × 10−3 | −63.2 (−71.0, −53.2) |
3.4 × 10−16 |
| LPL | p.Asp36Asn | rs1801177 | G/A | 1.22 | 0.054 (−0.010, 0.119) |
0.099 | −0.086 (−0.112, −0.060) |
1.4 × 10−10 | 9.5 (6.4, 12.7) |
7.0 × 10−10 |
| LPL | p.Asn318Ser | rs268 | A/G | 1.14 | 0.042 (−0.024, 0.109) |
0.21 | −0.10 (−0.13, −0.08) |
1.1 × 10−13 | 12.0 (8.7, 15.4) |
1.5 × 10−13 |
| ABCA1 a | Splice region | rs188308962 | A/G | 0.35 | −0.17 (−0.30, −0.05) |
6.3 × 10−3 | −0.23 (−0.28, −0.18) |
2.2 × 10−19 | −4.2 (−9.3, 1.3) |
0.13 |
| NR1H3 a | Splice region | rs200557846 | C/A | 0.61 | −0.006 (−0.096, 0.084) |
0.90 | 0.12 (0.08, 0.16) |
7.2 × 10−10 | −5.6 (−9.4, −1.7) |
5.6 × 10−3 |
| APOC3 | Splice donor | rs138326449 | G/A | 0.23 | −0.51 (−0.66, −0.36) |
2.4 × 10−11 | 0.34 (0.28, 0.40) |
1.2 × 10−27 | −44.6 (−48.3, −40.8) |
7.2 × 10−66 |
| APOA1 a | p.Val43Leu | 11:116837074 | C/G | 0.70 | −0.16 (−0.25, −0.08) |
2.5 × 10−4 | 0.17 (0.14, 0.21) |
4.5 × 10−22 | 5.2 (1.2, 9.4) |
0.01 |
| MAP1A | p.Pro2349Leu | rs55707100 | C/T | 2.76 | 0.017 (−0.028, 0.061) |
0.47 | −0.046 (−0.063, −0.028) |
3.1 × 10−7 | 6.8 (4.7, 8.9) |
3.8 × 10−11 |
| LIPC a | p.Arg208His | rs200684324 | G/A | 0.18 | 0.15 (−0.02, 0.31) |
0.079 | 0.19 (0.13, 0.26) |
1.3 × 10−8 | 14.2 (6.1, 22.8) |
4.1 × 10−4 |
| CETP a | p.Val39Glyfs | 16:56962092 | T/TG | 0.06 | −0.53 (−0.81, −0.25) |
2.4 × 10−4 | 0.40 (0.29, 0.52) |
5.4 × 10−12 | −5.0 (−16.6, 8.2) |
0.44 |
| CETP a | p.Glu443Lys | rs536221680 | G/A | 0.29 | −0.31 (−0.45, −0.18) |
6.3 × 10−6 | 0.33 (0.28, 0.39) |
4.4 × 10−32 | −0.2 (−5.6, 5.6) |
0.96 |
| CETP | p.Arg468Gln | rs1800777 | G/A | 3.57 | 0.10 (0.06, 0.13) |
1.3 × 10−6 | −0.18 (−0.19, −0.16) |
7.4 × 10−108 | 2.2 (0.5, 4.0) |
0.01 |
| LCAT | p.Ser232Thr | rs4986970 | A/T | 2.90 | 0.00 (−0.043, 0.043) |
0.99 | −0.048 (−0.066, −0.031) |
5.2 × 10−8 | 0.4 (−1.5, 2.4) |
0.67 |
| CD300LG | p.Arg82Cys | rs72836561 | C/T | 3.36 | 0.045 (0.005, 0.084) |
0.026 | −0.087 (−0.103, −0.071) |
3.2 × 10−26 | 6.7 (4.8, 8.6) |
7.3 × 10−13 |
| ABCA6 | p.Cys1359Arg | rs77542162 | A/G | 2.55 | 0.15 (0.10, 0.19) |
5.4 × 10−11 | −0.007 (−0.025, 0.010) |
0.41 | −2.6 (−4.5, −0.6) |
0.01 |
| LIPG | p.Asn396Ser | rs77960347 | A/G | 1.17 | 0.16 (0.10, 0.23) |
1.2 × 10−6 | 0.13 (0.10, 0.15) |
1.0 × 10−20 | 3.5 (0.6, 6.6) |
0.019 |
| ANGPTL4 | p.Glu40Lys | rs116843064 | G/A | 2.39 | −0.16 (−0.21, −0.11) |
8.7 × 10−11 | 0.10 (0.08, 0.12) |
3.9 × 10−23 | −11.9 (−13.7, −9.9) |
1.4 × 10−30 |
| LDLR | Splice donor | rs200238879 | T/C | 0.056 | 1.39 (1.12, 1.66) |
1.7 × 10−23 | −0.054 (−0.165, 0.057) |
0.34 | −12.0 (−22.1, −0.6) |
0.04 |
| LDLR a | Splice region | rs72658867 | G/A | 2.22 | −0.42 (−0.47, −0.37) |
5.2 × 10−63 | 0.029 (0.009, 0.049) |
4.2 × 10−3 | −1.8 (−3.9, 0.4) |
0.11 |
| APOC1 a | Intronic | rs539667984 | G/C | 0.82 | −0.12 (−0.20., −0.04) |
3.0 × 10−3 | 0.11 (0.07, 0.14) |
1.8 × 10−10 | −13.6 (−16.7, −10.4) |
4.0 × 10−15 |
| HNF4A | p.Thr139lle | rs1800961 | C/T | 4.60 | −0.04 (−0.072, −0.008) |
0.013 | −0.065 (−0.079, −0.051) |
5.2 × 10−20 | 1.0 (−0.5, 2.5) |
0.21 |
Effect (in mmol/L or percent change for log-transformed triglyceride levels) is given with respect to allele A2. Variant type was determined on the basis of information from Ensembl release 70 using Variant Effect Predictor (VEP) version 2.8. For variants without an rsID, the chromosomal position (chr:position) in Build 38 of the human reference sequence is given. Non-HDL-C, non-HDL cholesterol; HDL-C, HDL cholesterol; A1/A2, major allele/minor allele; A2 (%), frequency of allele A2; Cl, confidence interval.
a
New sequence variant.