Implications of discoveries from genome-wide association studies in current cardiovascular practice

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.