Table 3.
Single nucleotide polymorphisms associated with high-density lipoprotein cholesterol identified through genome-wide association studie
Chromosome | Strongest SNP | Chromosome position | Sample size | MAF (average) | Change in HDLc/β | Pvalue | Proximal gene | Ref. |
1 | rs2144300 | 228 361 539 | 8656 | 40 | - | 6.6 × 10-7 | GALNT2 | [20] |
rs4846914 | 228 362 314 | 19 794 | 40 | -0.05 SD | 4.0 × 10-8 | [30] | ||
1 | rs4660293 | 39 800 767 | > 100 000 | 23 | -0.48 | 4.0 × 10-10 | PABPC4 | [28] |
1 | rs1689800 | 180 435 508 | > 100 000 | 35 | -0.47 | 3.0 × 10-10 | ZNF648 | [28] |
2 | rs1260326 | 27 584 444 | 16 682 | 41 | 0.93% | < 5 × 10-8 | GCKR | [31] |
2 | rs6754295 | 21 059 688 | 17 915 | 25 | 2.63 (z-sc)1 | 4.4 × 10-8 | APOB | [27] |
2 | rs2972146 | 226 808 942 | > 100 000 | 37 | 0.46 | 3.0 × 10-9 | IRS1 | [28] |
2 | rs10490964 | 51 926 908 | 18 245 | 12 | 1.35 mg/dL | 3.9 × 10-9 | COBLL1, GRB14 | [26] |
rs12328675 | 165 249 046 | > 100 000 | 13 | 0.68 | 3.0 × 10-10 | COBLL1 | [28] | |
4 | rs13107325 | 103 407 732 | > 100 000 | 7 | -0.84 | 7.0 × 10-11 | SLC39A8 | [28] |
5 | rs6450176 | 53 333 782 | > 100 000 | 26 | -0.49 | 5.0 × 10-8 | ARL15 | [28] |
6 | rs2814944 | 34 660 775 | > 100 000 | 16 | -0.49 | 4.0 × 10-9 | C6orf106 | [28] |
6 | rs605066 | 139 871 359 | > 100 000 | 42 | -0.39 | 3.0 × 10-8 | CITED2 | [28] |
6 | rs1084651 | 161 009 807 | > 100 000 | 16 | 1.95 | 3.0 × 10-8 | LPA | [28] |
7 | rs4731702 | 130 083 924 | > 100 000 | 48 | 0.59 | 1.0 × 10-15 | KLF14 | [28] |
8 | rs2083637 | 19 909 455 | 17 922 | 26 | 4.14 (z-sc)1 | 5.5 × 10-18 | LPL | [27] |
rs10503669 | 19 891 970 | 8656 | 10 | 3.2 × 10-10 | [20] | |||
rs331 | 19 864 685 | 6382 | 28 | 1.5 mg/dL | 9.1 × 10-7 | [32] | ||
rs17482753 | 19 876 926 | 8180 | - | 2.8 × 10-11 | [33] | |||
rs326 | 19 863 719 | 10 536 | 22-30 | 1.8 × 10-8 | [35] | |||
rs331 | 19 864 685 | 6382 | 28 | 1.5 mg/dL | 9.1 × 10-7 | [32] | ||
rs12678919 | 19 888 502 | 19 794 | 10 | 0.23 SD | 2.0 × 10-34 | [30] | ||
rs301 | 19 861 214 | 5592 | 25 | 0.04 | 9.3 × 10-11 | [36] | ||
8 | rs3916027 | 19 869 148 | 5592 | 27 | 0.04 | 5.4 × 10-10 | SLC18A1 | [36] |
8 | rs331 | 19 864 685 | 16 809 | 27 | 0.43% | < 5 × 10-8 | Intergenic, PPP1R3B, LPL | [31] |
rs9987289 | 9 220 768 | > 100 000 | 9 | -1.21 | 6.0 × 10-25 | PPP1R3B | [25] | |
8 | rs2293889 | 116 668 374 | > 100 000 | 0.41 | -0.44 | 6.0 × 10-11 | TRPS1 | [28] |
9 | r1323432 | 103 402 758 | 8656 | 12 | 1.93 mg/dL | 2.5 × 10-8 | GRIN3A | [20] |
9 | rs3905000 | 106 696 891 | 17 913 | 14 | -4.37 (z-sc)1 | 8.6 × 10-13 | ABCA1 | [27] |
rs4149268 | 106 687 041 | 8656 | 36 | 3.3 × 10-7 | [20] | |||
rs3890182 | 106 687 476 | 21 312 | - | 3.0 × 10-10 | [29] | |||
rs9282541 | 106 660 656 | 10 536 | 0-9 | 4.8 × 10-8 | [35] | |||
rs2515614 | 106 724 139 | 16 798 | 34 | 0.20% | < 5 × 10-8 | [31] | ||
rs1883025 | 106 704 122 | 19 371 | 26 | -0.08 SD | 1.0 × 10-9 | [30] | ||
9 | rs471364 | 15 279 578 | 40 414 | 12 | -0.08 SD | 3.0 × 10-10 | TTC39B | [29] |
rs581080 | 15 295 378 | > 100 000 | 18 | -0.65 | 3.0 × 10-12 | [28] | ||
9 | rs1883025 | 106 704 122 | > 100 000 | 25 | -0.94 | 2.0 × 10-33 | ABCA1 | [28] |
11 | rs12225230 | 116 233 840 | 6382 | 18 | 1.5 mg/dL | 5.3 × 10-5 | APOA1/C3/A4/A5 | [32] |
rs618923 | 116 159 369 | 12 111 | 25 | 0.30% | < 5 × 10-8 | [31] | ||
rs964184 | 116 154 127 | 19 794 | 14 | -0.17 SD | 1.0 × 10-12 | [30 | ||
rs7350481 | 116 091 493 | 8993 | 28 | 0.62% | 8.8 × 10-10 | [36] | ||
rs7350481 | 116 091 493 | 18 245 | 2.8 × 10-12 | [26] | ||||
11 | rs2923084 | 10 345 358 | > 100 000 | 17 | -0.41 | 5.0 × 10-8 | AMPD3 | [28] |
11 | rs3136441 | 46 699 823 | > 100 000 | 15 | 0.78 | 3.0 × 10-18 | LRP4 | [28] |
11 | rs7395662 | 17 917 | 39 | 2.82 (z-sc)1 | 6.0 × 10-11 | MADD-FOLH1 | [27] | |
11 | rs174547 | 61 327 359 | 40 330 | 33 | -0.09 SD | 2.0 × 10-12 | FADS1-S3 | [30] |
11 | rs6589565 | 116 145 447 | 5592 | -0.05 | 4.4 × 10-7 | BUD13 | [36] | |
11 | rs2075290 | 116 158 506 | 5592 | 7 | -0.05 | 4.2 × 10-7 | ZNF259 | [36] |
12 | rs2338104 | 108 379 551 | 8656 | 45 | 1.9 × 10-6 | MVK/MMAB | [20] | |
rs2338104 | 108 379 551 | 19 793 | 45 | -0.07 SD | 1.0 × 10-10 | [30] | ||
rs7134594 | 108 484 574 | > 100 000 | 47 | -0.44 | 7.0 × 10-15 | [28] | ||
12 | rs7134375 | 20 365 025 | > 100 000 | 42 | 0.40 | 4.0 × 10-8 | PDE3A | [28] |
12 | rs4759375 | 122 362 191 | > 100 000 | 6 | 0.86 | 7.0 × 10-9 | SBNO1 | [28] |
12 | rs4765127 | 123 026 120 | > 100 000 | 34 | 0.44 | 3.0 × 10-10 | ZNF664 | [28] |
12 | rs838880 | 123 827 546 | > 100 000 | 31 | 0.61 | 3.0 × 10-14 | SCARB1 | [28] |
12 | rs1818702 | 102 047 685 | 16 844 | 29 | 0.22% | < 5 × 10-8 | Intergenic, ASCL1, PAH | [31] |
15 | rs1532085 | 56 470 658 | 19 736 | 41 | 5.03 (z-sc)1 | 9.7 × 10-36 | LIPC | [27] |
rs4115041 | 121 186 681 | 8656 | 33 | 2.8 × 10-9 | [20] | |||
rs1532085 | 56 470 658 | 6382 | 37 | 1.8 mg/dL | 1.3 × 10-10 | [32] | ||
rs1800588 | 56 510 967 | 21 312 | - | 2.0 × 10-32 | [29] | |||
rs11858164 | 56 530 023 | 10 536 | 27-55 | 7.0 × 10-8 | [35] | |||
rs1532085 | 56 470 658 | 6382 | 37 | 1.8 mg/dL | 1.3 × 10-10 | [32] | ||
rs1800588 | 56 510 967 | 16 811 | 22 | 0.60% | < 5 × 10-8 | [31] | ||
rs10468017 | 56 465 804 | 19 794 | 30 | 0.10 SD | 8.0 × 10-23 | [30] | ||
rs1077834 | 56 510 771 | 5987 | 49 | 1.00% | 1.3 × 10-14 | [36] | ||
rs1077834 | 56 510 771 | 18 245 | 1.4 × 10-23 | [26] | ||||
rs261342 | 56 518 445 | 5592 | 22 | 0.03 | 6.3 × 10-8 | [36] | ||
rs1532085 | 56 470 658 | > 100 000 | 39 | 1.45 | 3.0 × 10-96 | [28] | ||
15 | rs2652834 | 61 183 920 | > 100 000 | 20 | -0.39 | 9.0 × 10-9 | LACTB | [28] |
16 | rs1800775 | 55 552 737 | 2623 | 47 | 2.5 × 10-13 | CETP | [28] | |
rs1532624 | 55 562 980 | 19 674 | 43 | 8.24 (z-sc)1 | 9.4 × 10-94 | [27] | ||
rs3764261 | 55 550 825 | 8656 | 31 | 2.42 mg/dL | 2.8 × 10-19 | [20] | ||
rs3764261 | 55 550 825 | 6382 | 31 | 4.0 mg/dL | 1.0 × 10-41 | [32] | ||
rs1800775 | 55 552 737 | 2758 | 49 | 2.6 mg/dL | 3.0 × 10-13 | [29] | ||
rs1800775 | 55 552 737 | 1643 | 47 | 3.99 mg/dL | 6.1 × 10-15 | [33] | ||
rs9989419 | 55 542 640 | 8216 | - | 8.5 × 10-27 | [33] | |||
rs7205804 | 55 562 390 | 10 536 | 37-50 | 4.7 × 10-47 | [36] | |||
rs3764261 | 55 550 825 | 6382 | 31 | 4.0 mg/dL | 1.0 × 10-41 | [32] | ||
rs1800775 | 55 552 737 | 16 779 | 49 | 2.50% | < 5 × 10-8 | [31] | ||
rs3764261 | 55 550 825 | 322 | - | 6.2 mg/dL | 3.4 × 10-12 | [39] | ||
rs3764261 | 55 550 825 | 18 245 | 3.7 × 10-93 | [26] | ||||
rs173539 | 55 545 545 | 19 794 | 32 | 0.25 SD | 4.0 × 10-75 | [30] | ||
rs3764261 | 55 550 825 | 5987 | 21 | 2.11% | 4.8 × 10-29 | [37] | ||
rs3764261 | 55 550 825 | 18 245 | 30-48 | 3.7 × 10-93 | [27] | |||
rs17231506 | 55 552 029 | 5592 | 32 | 0.07 | 2.3 × 10-36 | [36] | ||
rs3764261 | 55 550 825 | > 100 000 | 32 | 3.39 | 7.0 × 10-380 | [28] | ||
16 | rs255052 | 66 582 496 | 8656 | 17 | 1.5 × 10-6 | LCAT | [20] | |
rs255052 | 66 582 496 | 8656 + 4534 | - | 1.2 × 10-7 | [20] | |||
rs2271293 | 66 459 571 | 31 946 | 11 | 0.07 SD | 9.0 × 10-13 | [30] | ||
rs16942887 | 66 485 543 | > 100 000 | 12 | 1.27 | 8.0 × 10-33 | [28] | ||
16 | rs2271293 | 66 459 571 | 17 910 | 13 | 4.99 (z-sc)1 | 8.3 × 10-16 | CTCF-PRMT8 | [27] |
16 | rs289743 | 55 575 29 | 5592 | 31 | 0.03 | 8.6 × 10-9 | NLRC5 | [36] |
16 | rs2925979 | 80 092 291 | > 100 000 | 30 | -0.45 | 2.0 × 10-11 | CMIP | [28] |
17 | rs11869286 | 35 067 382 | > 100 000 | 34 | -0.48 | 1.0 × 10-13 | STARD3 | [28] |
17 | rs4148008 | 64 386 889 | > 100 000 | 32 | -0.42 | 2.0 × 10-10 | ABCA8 | [28] |
17 | rs4129767 | 73 915 579 | > 100 000 | 49 | -0.39 | 8.0 × 10-9 | PGS1 | [28] |
18 | rs4939883 | 45 421 212 | 16 258 | 17 | -3.98 (z-sc)1 | 1.6 × 10-11 | LIPG | [27] |
rs2156552 | 45 435 666 | 8656 | 16 | 8.4 × 10-7 | [20] | |||
rs2156552 | 45 435 666 | 21 312 | - | 2.0 × 10-7 | [29] | |||
rs4939883 | 45 421 212 | 16 648 | 16 | 0.22% | < 5 × 10-8 | [31] | ||
rs4939883 | 45 421 212 | 19 785 | 17 | -0.14 SD | 7.0 × 10-15 | [30] | ||
rs4939883 | 45 421 212 | 18 245 | 1.4 × 10-9 | [26] | ||||
rs7241918 | 45 414 951 | > 100 000 | 17 | -1.31 | 3.0 × 10-49 | [28] | ||
18 | rs12967135 | 56 000 003 | > 100 000 | 23 | -0.42 | 7.0 × 10-9 | MC4R | [28] |
19 | rs769449 | 50 101 842 | 16 728 | 12 | 0.30% | < 5 × 10-8 | APOC1-APOE | [31] |
18 245 | 2.6 × 10-11 | [26] | ||||||
19 | rs2967605 | 8 375 738 | 35 151 | 16 | -0.12 SD | 1.0 × 10-8 | ANGPTL3 | [30] |
rs7255436 | 8 339 196 | > 100 000 | 47 | -0.45 | 3.0 × 10-8 | [28] | ||
19 | rs737337 | 11 208 493 | > 100 000 | 8 | -0.64 | 3.0 × 10-9 | LOC55908 | [28] |
19 | rs386000 | 59 484 573 | > 100 000 | 20 | 0.83 | 4.0 × 10-16 | LILRA3 | [28] |
20 | rs6065906 | 43 987 422 | 16 810 | 48 | 0.40% | < 5 × 10-8 | PLTP | [31] |
18 245 | 1.9 × 10-14 | [26] | ||||||
20 | rs1800961 | 42 475 778 | 30 714 | 3 | -0.19 SD | 8.0 × 10-10 | HNF4A | [30] |
rs1800961 | 42 475 778 | > 100 000 | 3 | -1.88 | 1.0 × 10-15 | [28] | ||
20 | rs7679 | 44 009 909 | 40 248 | 19 | -0.07 SD | 4.0 × 10-9 | PLTP | [30] |
rs6065906 | 43 987 422 | > 100 000 | 18 | -0.93 | 2.0 × 10-22 | [28] | ||
22 | rs181362 | 20 262 068 | > 100 000 | 20 | -0.46 | 1.0 × 10-8 | UBE2L3 | [28] |
1z-sc: the ENGAGE consortium provided the effect size on the z-scale. GALNT2: N-acetylgalactosaminyltransferase 2; PABPC4: Poly(A) binding protein, cytoplasmic 4 (inducible form); ZNF648: Zinc finger protein 648; GCKR: Glucokinase (hexokinase 4) regulator; APOB: Apolipoprotein B; IRS1: Insulin receptor substrate 1; COBLL1: COBL-like 1; GRB14: Growth factor receptor-bound protein 14; SLC39A8: Solute carrier family 39 (zinc transporter) member 8; ARL15: ADP-ribosylation factor-like 15; C6orf106: Chromosome 6 open reading frame 106; CITED2: Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain 2; LPA: Lipoprotein, Lp(a); KLF14: Kruppel-like factor 14; LPL: Lipoprotein lipase; SLC18A1: Solute carrier family 18 (vesicular monoamine) member 1; PPP1R3B: Protein phosphatase 1, regulatory (inhibitor) subunit 3B; TRPS1: Trichorhinophalangeal syndrome 1; GRIN3A: Glutamate receptor, ionotropic, N-methyl-D-aspartate 3A; ABCA1: ATP-binding cassette, sub-family A (ABC1) member 1; TTC39B: Tetratricopeptide repeat domain 39B; ABCA1: ATP-binding cassette, sub-family A (ABC1) member 1; APOA1: Apolipoprotein A-I; AMPD3: Adenosine monophosphate deaminase 3; LRP4: Low density lipoprotein receptor-related protein 4; MADD-FOLH1: MAP-kinase activating death domain- folate hydrolase (prostate-specific membrane antigen) 1; FADS1-S3: Fatty acid desaturase 1; BUD13: BUD13 homolog; ZNF259: Zinc finger protein 259; MVK: Mevalonate kinase; MMAB: Methylmalonic aciduria (cobalamin deficiency) cblB type; PDE3A: Phosphodiesterase 3A; SBNO1: Strawberry notch homolog 1; ZNF664: Zinc finger protein 664; SCARB1: Scavenger receptor class B member 1; ASCL1: Achaete-scute complex homolog 1; PAH: Phenylalanine hydroxylase; LIPC: Hepatic lipase; LACTB: Lactamase β; CETP: Cholesteryl ester transfer protein plasma; LCAT: Lecithin-cholesterol acyltransferase; CTCF: CCCTC-binding factor (zinc finger protein); PRMT8: Protein arginine methyltransferase 8; NLRC5: NLR family CARD domain containing 5; STARD3: StAR-related lipid transfer (START) domain containing 3; ABCA8: ATP-binding cassette; sub-family A (ABC1) member 8; PGS1: Phosphatidylglycerophosphate synthase 1; LIPG: Lipase endothelial; MC4R: Melanocortin 4 receptor; APOC1: Apolipoprotein C-I; APOE: Apolipoprotien E; ANGPTL3: Angiopoietin-like 3; LILRA3: Leukocyte immunoglobulin-like receptor, subfamily A (without TM domain) member 3; PLTP: Phospholipid transfer protein; HNF4A: Hepatocyte nuclear factor 4 α; PLTP: Phospholipid transfer protein; UBE2L3: Ubiquitin-conjugating enzyme E2L 3; SNP: Single nucleotide polymorphisms; MAF: Minor allele frequency. HDLc: high-density lipoprotein cholesterol.