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

Table 1 Single Nucleotide Polymorphisms associated with coronary heart disease in genome-wide association studies

Chromosome	SNP	Position	Sample size	MAF (%)	OR (95% CI)	Pvalue	Proximal gene	Ref.
1	rs646776	109 620 053	9746/9746	81.0	1.17 (1.11-1.24)		CELSR2	[18,20,21]
	rs599839	109 623 689	2801/4582	-	1.29 (1.18-1.40)	4.05 × 10-9	PSRC1
	rs599839	109 623 689	1926/2938	80.8	1.20 (1.10-1.31)	1.30 × 10-5	SORT1
1	rs11206510	55 268 627	25 5381	81.0	1.15 (1.10-1.21)		PCSK9	[21]
1	rs17465637	220 890 152	9746/9746	72.0	1.13 (1.08-1.18)		MIA3	[18,21]
			2801/4582	-	1.20 (1.12-1.30)	1.27 × 10-6
2	rs6725887	203 454 130	9746/9746	14.0	1.17 (1.11-1.23)		WDR12	[21]
2	rs2943634	226 776 324	2801/4582	37/32	1.21 (1.03-1.30)	1.60 × 10-7	Intergenic	[18]
3	rs9818870	139 604 812	19 407/21 366	17.3/15.4	1.15 (1.11-1.19)	7.44 × 10-13	MRAS	[23]
6	rs12526453	13 035 530	25 5381	65.0	1.12 (1.08-1.17)		PHACTR1	[21]
6	rs6922269	151 294 678	2801/4582	30.0/26.0	1.23 (1.15-1.33)	2.90 × 10-8	MTHFD1L	[18]
	rs6922269	151 294 678	1926/2938	29.4/25.3	1.17 (1.04-1.32)	1.50 × 10-5
62	rs2048327	160 783 522	4976/4383	4.1/2.1	1.82 (1.57-2.12)	4.20 × 10-15	SLC22A3	[22]
	rs3127599	160 827 124					LPAL2
	rs7767084	160 882 493					LPA
	rs10755578	160 889 728
9	rs10757278	22 114 477	1607/6728	51.7/45.3	1.28 (1.22-1.35)	3.60 × 10-14	CDKN2A	[15,16,18,19,21,22,23,25]
	rs10757274	22 086 055	-	25.3/20.4	1.33 (1.23-1.47)		CDKN2B
	rs1333049	22 115 503	875/1644	54.0/48.0	1.33 (1.18-1.51)	3.40 × 10-6
	rs1333049	22 115 503	1926/2938	55.4/47.4	1.47 (1.27-1.70)	1.16 × 10-13	MTAP
	rs1333049	22 115 503	12 004/28 949	-	1.24 (1.20-1.28)
	-		9746/9746	56.0	1.28 (1.23-1.33)
	rs4977574	22 088 574	-	-	-
	-		19 407/21 366	-	-
	-		33 282	-	1.20 (1.08-1.34)3
	rs1333049	22 115 503
10	rs1746048	44 095 830	9746/9746	84.0	1.14 (1.08-1.21)		CXCL12	[18,21]
	rs501120	44 073 873	2801/4582	-/-	1.33 (1.20-1.48)	9.46 × 10-8
12	rs2259816	119 919 970	19 407/21 366	37.4/35.8	1.08 (1.05-1.11)		HNF1A-C12 or f43	[23]
16	rs4329913	55 462 933	18 245	-	1.29 (1.02-1.63)3		CETP	[26]
	rs7202364	55 342 891			0.76 (0.59-0.99)3
19	rs1122608	11 024 601	25 5381	75.0	1.15 (1.10-1.20)		LDLR	[20,21]
	rs6511720	11 063 306	1926/2938	90.2	1.29 (1.10-1.52)	6.70 × 10-4
19	rs4420638	50 114 786	1926/2938	20.9	1.17 (1.08-1.28)	1.00 × 10-4	APOE/C1/C4	[20,21]
	rs4420638	50 114 786	14 365/30 576
21	rs9982601	34 520 998	25 5381	13.0	1.28 (1.23-1.33)		MRPS6	[21]
							SLC5A3
							KCNE2

¹WTCC and GerMIFS I and GerMIFS II were added to the total sample; ²Haplotype CCTC; ³Hazard ratio per allele after adjustment for age and multiple risk factors. CELSR2: Cadherin EGF LAG seven-pass G-type receptor 2; PSRC1: Proline/serine-rich coiled-coil 1; SORT1: Sortilin 1; PCSK9: Proprotein convertase subtilisin/kexin type 9; MIA3: Melanoma inhibitory activity family member 3; WDR12: WD repeat protein 12; MRAS: Ras-related protein M-Ras; PHACTR1: Phosphatase and actin regulator 1; MTHFD1L: Methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1-like; SLC22A3: Solute carrier family 22 (extraneuronal monoamine transporter), member 3; LPAL2: Lipoprotein; Lp(a)-like 2 pseudogene; LPA: Lipoprotein Lp(a); CDKN2A: Cyclin-dependent kinase inhibitor 2A; CDKN2B: Cyclin-dependent kinase inhibitor 2B; MTAP: Methylthioadenosine phosphorylase; CXCL12: Chemokine (C-X-C motif) ligand 12; HNF1A-C12: Hepatocyte nuclear factor-1 homeobox A; CETP: Cholesteryl ester transfer protein plasma; LDLR: Low density lipoprotein receptor; APOE/C1/C4: Apolipoprotein; MRPS6: Mitochondrial ribosomal protein S6; SLC5A3: Solute carrier family 5 (sodium/myo-inositol cotransporter) member 3; KCNE2: Potassium voltage-gated channel subfamily E member 2; SNP: Single nucleotide polymorphisms; MAF: Minor allele frequency; OR: Odds ratio.

Table 2 Single nucleotide polymorphisms associated with total cholesterol identified through genome-wide association studies

Chromosome	Strongest SNP	Chromosome position	Sample size	MAF (average)	β	Pvalue	Proximal gene	Ref.
1	rs10903129	25 641 524	22 550	54	0.061	5.4 × 10-10	TMEM57	[27]
1	rs1167998	62 704 220	17 346	32	-0.073	6.4 × 10-10	DOCK7	[27]
	rs108889353		19 099	32	-0.079	3.7 × 10-12		[27]
1	rs646776	109 620 053	17 441	22	-0.128	8.5 × 10-22	CELSR2	[27]
1	rs12027135	25 648 320	> 100 000	45	-1.22	4.0 × 10-11	LDLRAP1	[28]
1	rs7515577	92 782 026	> 100 000	21	-1.18	3.0 × 10-8	EVI5	[28]
1	rs2642442	219 040 186	> 100 000	48	-1.36	5.0 × 10-14	IRF2BP2	[28]
2	rs693	21 085 700	22 500	52	-0.096	8.7 × 10-23	APOB	[27]
2	rs6756629	43 918 594	17 472	92	0.145	1.5 × 10-11	ABCG5	[27]
2	rs7570971	135 554 376	> 100 000	34	1.25	2.0 × 10-8	RAB3GAP1	[28]
3	rs2290159	12 603 920	> 100 000	22	-1.42	4.0 × 10-9	RAF1	[28]
5	rs384662	35 421 429	20 873	44	0.092	2.5 × 10-19	HMGCR	[27]
	rs12916	74 692 295	> 100 000	39	2.84	9.0 × 10-47		[28]
5	rs6882076	156 322 875	> 100 000	35	-1.98	7.0 × 10-28	TIMD4	[28]
6	rs3177928	32 520 413	> 100 000	16	2.31	4.0 × 10-19	HLA	[28]
6	rs2814982	34 654 538	> 100 000	11	-1.86	5.0 × 10-11	C6orf106	[28]
6	rs9488822	116 419 586	> 100 000	35	-1.18	2.0 × 10-10	FRK	[28]
7	rs12670798	21 573 877	> 100 000	23	1.43	9.0 × 10-10	DNAH11	[28]
7	rs2072183	44 545 705	> 100 000	25	2.01	3.0 × 10-11	NPC1L1	[28]
8	rs6987702	126 573 908	17 413	29	0.073	3.3 × 10-9	TRIB1	[27]
8	rs2081687	59 551 119	> 100 000	35	1.23	2.0 × 10-12	CYP7A1	[28]
8	rs2737229	116 717 740	> 100 000	30	-1.11	2.0 × 10-8	TRPS1	[28]
10	rs2255141	113 923 876	> 100 000	30	1.14	2.0 × 10-10	GPAM	[28]
11	rs174570	61 353 788	20 916	83	0.088	1.5 × 10-10	FADS2/3	[27]
11	rs10128711	18 589 560	> 100 000	28	-1.04	3.0 × 10-8	SPTY2D1	[28]
11	rs7941030	122 027 585	> 100 000	38	0.97	2.0 × 10-10	UBASH3B	[28]
12	rs11065987	110 556 807	> 100 000	42	-0.96	7.0 × 10-12	BRAP	[28]
12	rs1169288	119 901 033	> 100 000	33	1.42	1.0 × 10-14	HNF1A	[28]
16	rs2000999	70 665 594	> 100 000	20	2.34	3.0 × 10-24	HPR	[28]
19	rs2228671	11 071 912	20 910	88	0.158	9.3 × 10-24	LDLR	[27]
19	rs2304130	19 650 528	20 914	7	-0.153	2.0 × 10-15	NCAN	[27]
19	rs2075650	50 087 459	17 463	15	0.138	2.9 × 10-19	TOMM40-APOE	[27]
	rs157580	50 087 106	20 903	33	-0.09	5.1 × 10-17		[27]
19	rs10401969	19 268 718	> 100 000	7	-4.74	3.0 × 10-38	CILP2	[28]
19	rs492602	53 898 229	> 100 000	49	1.27	2.0 × 10-10	FLJ36070	[28]
20	rs2277862		> 100 000	15	-1.19	4.0 × 10-10	ERGIC3	[28]
20	rs2902940	38 524 901	> 100 000	29	-1.38	6.0 × 10-11	MAFB	[28]

TMEM57: Transmembrane protein 57; DOCK7: Dedicator of cytokinesis 7; CELSR2: Cadherin, EGF LAG seven-pass G-type receptor 2; LDLRAP1: Low density lipoprotein receptor adaptor protein 1; EVI5: Ecotropic viral integration site 5; IRF2BP2: Interferon regulatory factor 2 binding protein 2; APOB: Apolipoprotein B; ABCG5: ATP-binding cassette sub-family G member 5; RAB3GAP1: RAB3 GTPase activating protein subunit 1 (catalytic); RAF1: v-raf-1 murine leukemia viral oncogene homolog 1; HMGCR: 3-hydroxy-3-methylglutaryl-CoA reductase; TIMD4: T-cell immunoglobulin and mucin domain containing 4; HLA: Human leukocyte antigen (HLA) complex; C6orf106: Chromosome 6 open reading frame 106; FRK: Fyn-related kinase; DNAH11: Dynein, axonemal, heavy chain 11; NPC1L1: NPC1 (Niemann-Pick disease, type C1, gene)-like 1; TRIB1: Tribbles Homolog-1 (Trib1); CYP7A1: Cytochrome P450, family 7, subfamily A, polypeptide 1; TRPS1: Trichorhinophalangeal syndrome 1; GPAM: Glycerol-3-phosphate acyltransferase; mitochondrial; FADS: Fatty acid desaturase; SPTY2D1: Suppressor of Ty, domain containing 1 (S. cerevisiae); UBASH3B: Ubiquitin associated and SH3 domain containing B; BRAP: BRCA1 associated protein; HNF1A: Hepatocyte nuclear factor-1 α; HPR: Haptoglobin-related protein; LDLR: Low density lipoprotein receptor; NCAN: Neurocan; TOMM40: Translocase of outer mitochondrial membrane 40 homolog; CILP2: Cartilage intermediate layer protein 2; ERGIC3: Endoplasmic reticulum-Golgi intermediate compartment protein 3; MAFB: V-maf musculoaponeurotic fibrosarcoma oncogene homolog B; SNP: Single nucleotide polymorphisms; MAF: Minor allele frequency.

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.

Table 4 Single nucleotide polymorphisms associated with low-density lipoprotein cholesterol identified through genome-wide association studies

Chromosome	Strongest SNP	Chromosome position	Sample size	MAF (average)	β	Pvalue	Proximal gene	Ref.
1	rs1167998	62 704 220	12 685	22	-0.155	7.8 × 10-23	PSRC1, CELSR2, SORT1	[27]
	rs646776	109 620 053	6382	22	-	4.9 × 10-19		[32]
	rs599839	109 623 689	1636	24	-	1.1 × 10-7		[34]
	rs602633	109 623 034	8589	20	-	4.8 × 10-14		[20]
	rs646776	109 620 053	16 791	22	-0.04	< 5 × 10-8	CELSR2	[31]
	rs646776	109 620 053	21 312	24	-0.16	5 × 10-42	PSRC1	[29]
	rs12740374	109 619 113	19 648	21	-0.23	2.0 × 10-42		[30]
	rs599839	109 623 689	11 685	21	-0.05	1.7 × 10-15		[40]
	rs646776	109 620 053	4337	21	-0.16	4.3 × 10-9		[40]
	rs12740374	109 619 113	5592	21	-0.15	1.8 × 10-9	SORT1	[36]
	rs646776	109 620 053	5592	22	-0.14	3.8 × 10-8		[36]
	rs629301	109 619 829	> 100 000	22	-5.65	1.0 × 10-170		[28]
1	rs11591147	55 278 235	16 826	2	-0.12	< 5 × 10-8	PCSK9	[31]
	rs11591147	55 278 235	12 167	2	-0.13	< 5 × 10-8		[31]
	rs11591147	55 278 235	21 312	1	-0.26	2.0 × 10-24		[30]
	rs11206510	55 268 627	19394			3.5 × 10-11		[20]
	rs11206510	55 268 627	19 629	19	-0.09	4.0 × 10-8		[30]
	rs11591147	55 278 235	5592		-0.55	9.3 × 10-12		[36]
	rs2479409	55 277 238	> 100 000	30	2.01	2.0 × 10-28		[28]
2	rs693	21 085 700	2601	22		7.1 × 10-7	APOB	[38]
	rs562338	21 141 826	1636 + 2631	17		8.6 × 10-13		[34]
	rs515135	21 139 562	8589	83		3.1 × 10-14		[20]
	rs562338	21 141 826	8589 + 10 849			5.6 × 10-22		[20]
	rs693	21 085 700	16 112	52	-0.098	3.6 × 10-17		[28]
	rs506585	21 250 687	6382	20	-4.6	9.3 × 10-9		[32]
	rs506585	21 250 687	16 842	20	-0.04	< 5 × 10-8		[31]
	rs693	21 085 700	21 312	48	0.12	1.0 × 10-21		[29]
	rs515135	21 139 562	19 648	20	-0.16	5.0 × 10-29		[30]
	rs562338	21 141 826	11 685	20	-0.04	1.4 × 10-9		[40]
	rs1713222	21 124 828	4337	16	-0.17	1.0 × 10-8		[40]
	rs562338	21 141 826	5592	18	-0.18	1.2 × 10-11		[36]
	rs1367117	21 117 405	> 100 000	30	4.05	4.0 × 10-114		[28]
2	rs6756629	43 918 594	12 706	92	0.157	2.6 × 10-10	ABCG5	[27]
2	rs6544713	43 927 385	23 456	32	0.15	2 × 10-20	ABCG8	[30]
	rs4299376	43 926 080	> 100 000	30	2.75	2.0 × 10-47	ABCG5/8	[28]
2	rs780094	27 594 741	16 841	40	0.03	< 5 × 10-8	GCKR	[31]
5	rs1501908	156 330 747	27 280	37	-0.07	1 × 10-11	TIMD4-HAVCR1	[30]
5	rs3846662	74 686 840	16 135	44	0.079	1.5 × 10-11	HMGCR	[27]
	rs12654264	74 684 359	2758 + 18 554	39	0.1	1.0 × 10-20		[29]
	rs3846663	74 691 482	19 648	38	0.07	8.0 × 10-12		[30]
	rs12654264	74 684 359	5592	38	0.11	5.8 × 10-8		[36]
6	rs3757354	88 570 980	> 100 000	22	-1.43	1.0 × 10-11	MYLIP	[28]
6	rs1800562	26 201 120	> 100 000	6	-2.22	6.0 × 10-10	HFE	[28]
6	rs1564348	160 498 850	> 100 000	17	-0.56	2.0 × 10-17	LPA	[28]
7	rs12670798	21 573 877	12 695	24	0.089	6.1 × 10-9	DNAH11	[27]
7	rs4731702	130 083 924	16 747	49	-0.02	< 5 × 10-8	KLF14	[31]
8	rs6982636	126 548 497	16 798	47	-0.02	< 5 × 10-8	TRIB1	[31]
8	rs11136341	145 115 531	> 100 000	40	1.4	4.0 × 10-13	PLEC1	[28]
9	rs9411489	135 144 821	> 100 000	20	2.24	6.0 × 10-13	ABO	[28]
11	rs174570	61 353 788	16 153	83	0.11	4.4 × 10-13	FADS2/3	[31]
11	rs3135506	116 167 617	16 837	6	-0.13	< 5 × 10-8	APOA1-A5	[31]
	rs2072560	116 167 036	5592	6	0.22	2.4 × 10-7		[36]
11	rs11220462	125 749 162	> 100 000	14	1.95	1.0 × 10-15	ST3GAL4	[28]
12	rs7307277	123 041 109	16 804	34	-0.02	< 5 × 10-8	CCDC92/DNAH10/ZNF664	[31]
12	rs2650000	119 873 345	39 340	36	0.07	2.0 × 10-8	HNF1A	[30]
14	rs8017377	51 667 587	> 100 000	47	1.14	5.0 × 10-1	NYNRIN	[28]
16	rs708272	55 553 789	16 843	43	-0.04	< 5 × 10-8	CETP	[31]
	rs17231506	55 552 029	5592	32	-0.11	5.0 × 10-7		[36]
17	rs7206971	42 780 114	> 100 000	49	0.78	2.0 × 10-8	OSBPL7	[28]
19	rs1699614	19 519 472	21 312	10	-0.1	3 × 10-8	NCAN, CILP2, PBX4	[29]
	rs2228603	19 190 924	8589	7		1.8 × 10-7		[20]
	rs16996148	19 519 472	19 394			2.7 × 10-9		[20]
	rs10401969	19 268 718	19 648	6	-0.05	2.0 × 10-8		[30]
19	rs688	11 088 602	4267	45		7.3 × 10-7	LDLR	[34]
	rs6511720	11 063 306	8589	9		6.8 × 10-10		[20]
	rs6511720	11 063 306	19 394			4.2 × 10-23		[20]
	rs2228671	11 071 912	16 148	82	0.136	4.2 × 10-14		[27]
	rs6511720	11 063 306	6382	12	-7.7	5.2 × 10-15		[32]
	rs6511720	11 063 306	16 843	12	-0.04	< 5 × 10-8		[31]
	rs6511720	11 063 306	21 312	10	-0.26	2 × 10-51		[29]
	rs6511720	11 063 306	19 648	10	-0.26	2.0 × 10-26		[30]
	rs2228671	11 071 912	4337	12	-0.18	1.1 × 10-8		[40]
	rs17248720	11 059 187	5592	13	-0.31	7.8 × 10-25		[36]
	rs6511720	11 063 306	> 100 000	11	6.99	4.0 × 10-117		[28]
19	rs2075650	50 087 459	12 697	15	0.16	9.3 × 10-19	TOMM40-APOE	[27]
	rs157580	50 087 106	16 160	68	-0.111	2.1 × 10-19		[27]
	rs2075650	50 087 459	4337	13	0.23	7.1 × 10-14		[40]
	rs2075650	50 087 459	5592	14	0.23	1.1 × 10-14		[36]
19	rs4420638	50 114 786	2601	22		3.4 × 10-13	APOC1-APOE	[38]
	rs4420638	50 114 786	4267	19		8.3 × 10-14		[34]
	rs4420638	50 114 786	8589	12		1.5 × 10-21		[20]
	rs4420638	50 114 786	19 394			3.0 × 10-43		[20]
	rs4803750	49 939 467	6382	7	-9.6	3.6 × 10-14		[32]
	rs4803750	49 939 467	16 616	7	-9.3	< 5 × 10-8		[32]
	rs4420638	50 114 786	21 312	20	0.19	1.0 × 10-60		[29]
	rs4420638	50 114 786	11 881	16	0.29	4.0 × 10-27		[30]
	rs4420638	50 114 786	11 685	18	0.06	1.2 × 10-20	APOC2	[40]
	rs12721046	50 113 094	5592	15	0.21	7.6 × 10-14		[36]
	rs12721109	50 139 061	5592	2	-0.54	5.1 × 10-14		[36]
	rs4420638	50 114 786	> 100 000	17	7.14	9.0 × 10-147	APOE	[28]
19	rs10402271	50 021 054	11 685	33	0.03	4.1 × 10-8	BCAM	[40]
	rs4605275	50 030 333	4337	31	-0.13	4.7 × 10-8		[40]
19	rs4803750	49 939 467	4337	7	-0.28	2.4 × 10-11	BCL3	[40]
	rs1531517	49 934 013	5592	7	-0.22	5.3 × 10-8		[36]
19	rs10402271	50 021 054	5592	33	0.15	2.1 × 10-12	PVRL2	[36]
20	rs6065906	43 987 422	16 843	48	0.02	< 5 × 10-8	PLPT	[31]
20	rs6102059	38 662 198	28 895	32	-0.06	4.0 × 10-9	MAFB	[30]
20	rs6029526	39 106 032	> 100 000	47	1.39	4.0 × 10-19	TOP1	[28]

β: Estimated mean; CELSR2: Cadherin EGF LAG seven-pass G-type receptor 2; PSRC1: Proline/serine-rich coiled-coil 1; SORT1: Sortilin 1; PCSK9: Proprotein convertase subtilisin/kexin type 9; APOB: Apolipoprotein B; ABCG: ATP-binding cassette sub-family G; GCKR: Glucokinase (hexokinase 4) regulator; TIMD4: T-cell immunoglobulin and mucin domain containing 4; HAVCR1: Hepatitis A virus cellular receptor 1; HMGCR: 3-hydroxy-3-methylglutaryl-CoA reductase; MYLIP: Myosin regulatory light chain interacting protein; HFE: Human hemochromatosis; LPA: Lipoprotein, Lp(a); DNAH11: Dynein axonemal heavy chain 11; KLF14: Kruppel-like factor 14; TRIB1: Tribbles homolog 1; PLEC1: Plectin; ABO: ABO blood group (transferase A, α 1-3-N-acetylgalactosaminyltransferase, transferase B, α 1-3-galactosyltransferase); FADS: Fatty acid desaturase; APOA1: Apolipoprotien A1; ST3GAL4: ST3 β-galactoside α-2,3-sialyltransferase 4; CCDC92: Coiled-coil domain containing 92; DNAH10: Dynein axonemal heavy chain 10; ZNF664: Zinc finger protein 664; HNF1A: HNF1 homeobox A; NYNRIN: NYN domain and retroviral integrase containing; CETP: Cholesteryl ester transfer protein plasma; OSBPL7: Oxysterol binding protein-like 7; NCAN: Nucleoporin 214 kDa; CILP2: Cartilage intermediate layer protein 2; PBX4: Pre-B-cell leukemia homeobox 4; LDLR: Low density lipoprotein receptor; TOMM40: Translocase of outer mitochondrial membrane 40 homolog; APOE: Apolipoprotien E; APOC2: Apolipoprotein C-II; APOE: Apolipoprotien E; BCAM: Basal cell adhesion molecule; BCL3: B-cell CLL/lymphoma 3; PVRL2: Poliovirus receptor-related 2 (herpesvirus entry mediator B); PLPT: Proteolipid protein; MAFB: V-maf musculoaponeurotic fibrosarcoma oncogene homolog B; TOP1: Topoisomerase (DNA) 1; SNP: Single nucleotide polymorphisms; MAF: Minor allele frequency.

Table 5 Single nucleotide polymorphisms associated with triglycerides identified through genome-wide association studies

Chromosome	Strongest SNP	Studies	Sample size	MAF (average)	β	Pvalue	Proximal gene	Ref.
1	rs1167998	62 704 220	14 268	32	-0.091	2.0 × 10-12	DOCK7	[27]
	rs10889353	62 890 784	14 337	32	-0.085	8.2 × 10-11		[27]
1	rs11591147	55 278 235	16 826	2	-0.09	< 5 × 10-8	PCSK9	[31]
1	rs12042319	62 822 407	4267	34		3.2 × 10-7	ANGPTL3	[34]
	rs10889353	62 890 784	16 831	33	-0.03	< 5 × 10-8		[31]
	rs10889353	62 890 784	8993	14	-0.13	2.0 × 10-9		[37]
	rs12130333	62 964 365	21 312	22	-0.11	2.0 × 10-8		[29]
	rs10889353	62 890 784	19 834	33	-0.05	3.0 × 10-7		[30]
	rs1748195	62 822 181	18 243			1.7 × 10-10		[20]
	rs2131925	62 798 530	> 100 000	32	-4.94	9.0 × 10-43		[28]
1	rs4846914	228 362 314	21 312	40	0.08	7.0 × 10-15	GALNT2	[28]
2	rs6754295	21 059 688	14 338	25	-0.077	2.5 × 10-8	APOB	[27]
	rs673548	21 091 049	12 694	76	0.086	1.1 × 10-8		[27]
	rs673548	21 091 049	16 797	21	-0.04	< 5 × 10-8		[31]
	rs693	21 085 700	21 312	48	0.12	1.0 × 10-21		[29]
	rs7557067	21 061 717	19 840	22	-0.08	9.0 × 10-12		[30]
	rs1042034	21 078 786	> 100 000	22	-5.99	1.0 × 10-45		[28]
2	rs780094	27 594 741	2659	35		3.7 × 10-8	GCKR	[38]
	rs780094	27 594 741	4267	39		8.1 × 10-14		[34]
	rs1260326	27 584 444	8684	40		1.5 × 10-15		[20]
	rs780094	27 594 741	18 243			6.1 × 10-32		[20]
	rs780094	27 594 741	17 790	63	-0.103	3.1 × 10-20		[27]
	rs1260326	27 584 444	6382	41	0.07	1.3 × 10-16		[32]
	rs1260326	27 584 444	16 650	41	0.07	< 5 × 10-8		[31]
	rs1260326	27 584 444	8993	45	-0.101	1.1 × 10-11		[37]
	rs780094	27 594 741	21 312	34	0.13	3.0 × 10-14		[29]
	rs1260326	27 584 444	19 840	45	0.12	2.0 × 10-31		[30]
	rs1260326	27 584 444	5592	40	0.06	1.8 × 10-7		[36]
	rs1260326	27 584 444	> 100 000	41	8.76	6.0 × 10-133		[28]
2	rs10195252	165 221 337	> 100 000	40	-2.01	2.0 × 10-10	COBLL1	[28]
3	rs645040	137 409 312	> 100 000	22	-2.22	3.0 × 10-8	MSL2L1	[28]
4	rs442177	88 249 285	> 100 000	41	-2.25	9.0 × 10-12	KLHL8	[28]
5	rs9686661	55 897 543	> 100 000	20	2.57	1.0 × 10-10	MAP3K1	[28]
6	rs2076530	32 471 794	16 829	43	0.03	< 5 × 10-8	BTNL2	[31]
6	rs2247056	31 373 469	> 100 000	25	-2.99	2.0 × 10-15	HLA	[28]
7	rs13238203	71 767 603	> 100 000	4	-7.91	1.0 × 10-9	TYW1B	[28]
7	rs17145738	72 620 810	2758 + 18 554	13	-0.14	7.0 × 10-22	BCL7B, TBL2, MLXIPL	[29]
							TBL2
	rs11974409	72 627 326	5592	20	-0.08	5.7 × 10-9	MLXIPL	[36]
	rs10551921	107 998 852	5592	20	-0.08	1.3 × 10-8		[36]
7	rs2240466	72 494 205	12 680	87	0.137	1.1 × 10-12	MLXIPL	[27]
	rs11974409	72 627 326	16 839	19	-0.04	< 5 × 10-8		[31]
	rs714052	72 502 805	19 840	12	-0.16	3.0 × 10-15		[30]
	rs17145738	72 620 810	18 243			2.0 × 10-12		[20]
	rs17145738	72 620 810	> 100 000	12	-9.32	6.0 × 10-58		[28]
7	rs4731702	130 083 924	16 714	49	-0.03	< 5 × 10-8	KLF14	[31]
7	rs17145713	72 542 746	5592	20	-0.09	5.3 × 10-10	BAZ1B	[36]
8	rs11776767	10 721 339	> 100 000	37	2.01	1.0 × 10-8	PINX1	[28]
8	rs1495741	18 317 161	> 100 000	22	2.85	5.0 × 10-14	NAT2	[28]
8	rs2083637	19 909 455	14 344	26	-0.107	1.0 × 10-14	LPL	[27]
	rs10096633	19 875 201	12 708	88	0.174	1.9 × 10-18		[27]
	rs12678919	19 888 502	19 840	10	-0.25	2.0 × 10-41		[30]
	rs10096633	19 875 201	8993	12	-0.169	9.3 × 10-14		[37]
	rs331	19 864 685	5592	25	-0.08	1.7 × 10-11		[36]
	rs12678919	19 888 502	> 100 000	12	-13.64	2.0 × 10-115		[28]
8	rs17482753	19 876 926	2652	11		4.9 × 10-7	LPL	[38]
	rs17482753	19 876 926	1636	10		1.2 × 10-9		[34]
	rs17482753	19 876 926	1636 + 2631			5.2 × 10-15		[34]
	rs6993414	19 947 198	8684	46		1.4 × 10-13		[20]
	rs10503669	19 891 970	4267			3.9 × 10-22		[20]
	rs328	19 864 004	6382	11	-0.09	4.7 × 10-11	Intergenic, PPP1R3B, LPL	[32]
	rs331	19 864 685	6382	28	-0.06	1.7 × 10-9		[32]
	rs328	19 864 685	16 812	11	-0.09	< 5 × 10-8	LPL	[31]
	rs328	19 864 004	21 242	9	-0.19	2.0 × 10-28		[29]
8	rs6982636	126 548 497	16 765	47	-0.03	< 5 × 10-8	TRIB1	[31]
	rs17321515	12 655 591	21 242	49	-0.08	4.0 × 10-17		[29]
	rs2954029	126 560 154	8684	56		2.8 × 10-8		[20]
	rs17321515	12 655 591	14 176			7.0 × 10-13		[20]
	rs2954029	126 560 154	19 840	44	-0.11	3.0 × 10-19		[30]
	rs2954029	126 560 154	> 100 000	47	-5.64	3.0 × 10-55		[28]
8	rs3916027	19 869 148	5592	27	-0.08	1.0 × 10-10	SLC18A1	[36]
8	rs7819412	11 082 571	33 336	48	-0.04	3.0 × 10-8	XKR6-AMAC1L2	[30]
10	rs10761731	64 697 616	> 100 000	43	-2.38	3.0 × 10-12	JMJD1C	[28]
10	rs2068888	94 829 632	> 100 000	46	-2.28	2.0 × 10-8	CYP26A1	[28]
11	rs12272004	116 108 934	12 622	7	-0.181	5.4 × 10-13	APO (A1/A4/A5/C3)	[27]
	rs6589566	116 157 633	1636	6		1.5 × 10-11		[34]
	rs6589566	116 157 633	1636 + 2631			3.7 × 10-12		[34]
	rs964184	116 154 127	8684	12		1.5 × 10-16		[20]
	rs12286037	116 157 417	18 422			1.0 × 10-26		[20]
	rs3135506	116 167 617	6382	6	0.13	5.5 × 10-12		[32]
	rs662799	116 168 917	6382	6	0.14	2.9 × 10-15		[32]
	rs3135506	116 167 617	16 804	6	0.14	< 5 × 10-8		[31]
	rs7350481	116 091 493	8993	43	0.24	1.4 × 10-49		[37]
	rs28927680	116 124 283	21 312	7	0.26	2.0 × 10-17		[29]
	rs964184	116 154 127	19 840	14	0.3	4.0 × 10-62		[30]
	rs651821	116 167 789	5592	6	0.21	8.8 × 10-21	APOA1	[36]
	rs964184	116 154 127	> 100 000	13	16.95	7.0 × 10-240		[28]
11	rs174547	61 327 359	38 846	33	0.06	2.0 × 10-14	FADS1-S3	[30]
	rs174546	61 326 406	> 100 000	34	3.82	5.0 × 10-24		[28]
11	rs6589565	116 145 447	5592	7	0.19	4.5 × 10-20	BUD13	[36]
11	rs2075290	116 158 506	5592	7	0.19	6.6 × 10-20	ZNF259	[36]
12	rs7307277	123 041 109	16 771	34	-0.04	< 5 × 10-8	CCDC92/DNAH10/	[31]
							ZNF664
12	rs11613352	-	> 100 000	23	-2.7	4.0 × 10-10	LRP1	[28]
15	rs2412710	40 471 079	> 100 000	2	7	2.0 × 10-8	CAPN3	[28]
15	rs2929282	42 033 223	> 100 000	5	5.13	2.0 × 10-11	FRMD5	[28]
15	rs4775041	56 461 987	8684	67		7.3 × 10-5	LIPC	[20]
	rs4775041	56 461 987	17 104			1.6 × 10-8		[20]
16	Rs11649653	30 825 988	> 100 000	40	-2.13	3.0 × 10-8	CTF1	[28]
16	rs1800775	55 552 737	16 779	49	-0.03	< 5 × 10-8	CETP	[31]
19	rs157580	50 087 106	16 160	33	-0.069	1.2 × 10-8	TOMM40-APOE	[27]
	rs439401	50 106 291	11 885	68	0.086	1.8 × 10-9		[27]
19	rs16996148	19 519 472	21 312	10	-0.1	4.0 × 10-9	NCAN, CILP2, PBX4	[29]
	rs10401969	19 268 718	8684	8		2.3 × 10-7		[20]
	rs16996148	19 519 472	18 391			2.5 × 10-9		[20]
	rs17216525	46 471 516	19 840	7	-0.11	4.0 × 10-11		[30]
	rs12610185	19 582 722	5592	9	-0.1	5.6 × 10-7		[36]
19	rs439401	50 106 291	16 638	35	-0.04	< 5 × 10-8	APOC1-APOE	[31]
	rs439401	50 106 291	> 100 000	36	-5.5	1.0 × 10-30	APOE	[28]
19	rs2304128	19 607 151	5592	9	-0.1	3.2 × 10-7	GMI	[36]
20	rs6065906	43 987 422	16 810	48	0.04	< 5 × 10-8	PLPT	[31]
	rs7679	44 009 909	38 561	19	0.07	7.0 × 10-11		[30]
22	rs5756931	36 875 979	> 100 000	40	-1.54	4.0 × 10-8	PLA2G6	[28]

β: Estimated mean; DOCK7: Dedicator of cytokinesis 7; PCSK9: Proprotein convertase subtilisin/kexin type 9; GALNT2: N-acetylgalactosaminyltransferase 2; ANGPTL3: Angiopoietin-like 3; APOB: Apolipoprotien B; GCKR: Glucokinase (hexokinase 4) regulator; COBLL1: COBL-like 1; MSL2L1: Male-specific lethal 2 homolog; KLHL8: Kelch-like 8; MAP3K1: Mitogen-activated protein kinase kinase kinase 1; BTNL2: Butyrophilin-like 2 (MHC class II associated); HLA: Major histocompatibility complex; TYW1B: tRNA-yW synthesizing protein 1 homolog B; TBL2: Transducin (β)-like 2; BCL7B: B-cell CLL/lymphoma 7B; TBL2: Transducin (β)-like 2; MLXIPL: MLX interacting protein-like; KLF14: Kruppel-like factor 14; BAZ1B: Bromodomain adjacent to zinc finger domain 1B; PINX1: PIN2/TERF1 interacting, telomerase inhibitor 1; NAT2: N-acetyltransferase 2 (arylamine N-acetyltransferase); LPL: Lipoprotein lipase; PP1R3B: Protein phosphatase 1, regulatory (inhibitor) subunit 3B; TRIB1: Tribbles homolog 1; SLC18A1: Solute carrier family 18 (vesicular monoamine) member 1; XKR6: XK Kell blood group complex subunit-related family member 6; AMAC1L2: Acyl-malonyl condensing enzyme 1-like 2; JMJD1C: Jumonji domain containing 1C; CYP26A1: Cytochrome P450 family 26 subfamily A polypeptide 1; APOA1: Apolipoprotein A-I; FADS: Fatty acid desaturase; CCDC92: Coiled-coil domain containing 92; DNAH10: Dynein axonemal heavy chain 10; ZNF664: Zinc finger protein 664; LRP1: Low density lipoprotein receptor-related protein 1; CAPN3: Calpain 3, (p94); FRMD5: FERM domain containing 5; LIPC: Hepatic lipase; CTF1: Cardiotrophin 1; CETP: Cholesteryl ester transfer protein plasma; TOMM40: Translocase of outer mitochondrial membrane 40 homolog; APOE: Apolipoprotien E; NCAN: Nucleoporin 214 kDa; CILP2: Cartilage intermediate layer protein 2; PBX4: Pre-B-cell leukemia homeobox 4; GMIP: GEM interacting protein; PLPT: Palmitoyl-protein thioesterase 1; PLA2G6: Phospholipase A2, group VI (cytosolic, calcium-independent); SNP: Single nucleotide polymorphisms; MAF: Minor allele frequency.

Table 6 Single nucleotide polymorphisms associated with hypertension and blood pressure in genome-wide association studies

Chr	SNP	Position	Ancestry	N (discovery)	Phenotype	Risk allele	Risk allele frequency	OR/β	P	Nearest gene	Ref.
1	rs17367504	11 785 365	E	34 433	SBP	G	0.14	-0.85	2 × 10-13	MTHFR, CLCN6, NPPA, NPPB, AGTRAP	[42,43]
2	rs6749447	168 749 632	E	542	SBP	G	0.28	1.90	8 × 10-5	STK39	[47]
3	rs9815354	41 887 655	E	29 136	DBP	A	0.17	0.49	3 × 10-9	ULK4	[42,43]
4	rs16998073	81 403 365	E	34 433	DBP	T	0.21	0.50	1 × 10-21	FGF5, PRDM8, C4orf22	[42,43]
4	rs991316	100 541 468	AA	1017	SBP	T	0.45	1.62	5 × 10-6	ADH7	[44]
10	rs11014166	18 748 804	E	29 136	DBP	A	0.66	0.37	1 × 10-8	CACNB2	[42,43]
10	rs1530440	63 194 597	E	34 433	DBP	T	0.19	-0.39	1 × 10-9	C10orf107, TMEM26, RTKN2, RHOBTB1, ARID5B, CYP17A1	[42,43]
10	rs1004467	104 584 497	E	29 136	SBP	A	0.90	1.05	1 × 10-10	TMEM26, RTKN2, RHOBTB1, ARID5B, CYP17A1	[42,43]
10	rs11191548	104 836 168	E	34 433	SBP	T	0.91	1.16	3 × 10-7	CYP17A1, AS3MT, CNNM2, NT5C2	[42,43]
11	rs381815	16 858 844	E	29 136	SBP	T	0.26	0.65	2 × 10-9	PLEKHA7	[42,43]
12	rs17249754	88584	EA	8842	SBP, DBP	A	0.37	1.06	9 × 10-7	ATP2B1	[49]
12	rs2681472	88 533 090	E	29 136	SBP, DBP, HTN	A	0.83	0.50	2 × 10-9	ATP2B1	[42,43]
12	rs2681492,	88 537 220	E	29 136	SBP, DBP, HTN	T	0.80	0.85	4 × 10-11	ATP2B1	[42,43]
12	rs3184504	110 368 991	E	29 136	SBP, DBP	T	0.49	0.48	3 × 10-14	ATXN2, SH2B3	[42,43]
12	rs653178	110 492 139	E	34 433	DBP	T	0.53	-0.46	3 × 10-18	ATXN2, SH2B3	[42,43]
12	rs2384550	113 837 114	E	29 136	DBP	A	0.35	0.43	4 × 10-8	TBX3, TBX5	[42,43]
15	rs1550576	56 000 706	AA	1017	SBP	C	0.86	1.92	3 × 10-6	ALDH1A2	[44]
15	rs1378942	72 865 396	E	34 433	DBP	C	0.36	0.43	1 × 10-23	CSK, CYP1A1, CYP1A2, LMAN1L, CPLX3, ARID3B, ULK3	[42,43]
15	rs6495122	72 912 698	E	29 136	DBP	A	0.42	0.40	2 × 10-10	CSK, CYP1A1, CYP1A2, LMAN1L, CPLX3, ARID3B, ULK3	[42,43]
16	rs13333226	20 273 155	E	3320	HTN	A	0.81	1.15	4 × 10-11	UMOD	[50]
16	rs11646213	81 200 152	E	1977	HTN	T	0.60	1.28	8 × 10-6	CDH13	[48]
17	rs12946454	40 563 647	E	34 433	SBP	T	0.28	0.57	1 × 10-8	PLCD3, ACBD4, HEXIM1, HEXIM2	[42,43]
17	rs16948048	44 795 465	E	34 433	DBP	G	0.39	0.31	5 × 10-9	ZNF652, PHB	[42,43]

E: European; AA: African American; EA: East Asians; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; HTN: Hypertension; ACBD4: Acyl-CoA binding domain containing 4; ADH7: Alcohol dehydrogenase 7 (class IV), mu or sigma polypeptide; AGTRAP: Angiotensin II receptor-associated protein; ALDH1A2: Aldehyde dehydrogenase 1 family, member A2; ARID5B: AT rich interactive domain 5B (MRF1-like); AS3MT: Arsenic (+3 oxidation state) methyltransferase; ATP2B1: ATPase; Ca⁺⁺ transporting; plasma membrane 1; ATXN2: Ataxin 2; C10orf107: Chromosome 10 open reading frame 107; C4orf22: Chromosome 4 open reading frame 22; CACNB2: Calcium channel, voltage-dependent, β 2 subunit; CDH13: Cadherin 13, H-cadherin (heart); CLCN6: Chloride channel 6; CNNM2: Cyclin M2; CPLX3: Complexin 3; CSK: C-src tyrosine kinase; CYP17A1: Cytochrome P450, family 17, subfamily A, polypeptide 1; CYP1A1: Cytochrome P450; family 1, subfamily A, polypeptide 1; CYP1A2: Cytochrome P450, family 1, subfamily A, polypeptide 2; FGF5: Fibroblast growth factor 5; HEXIM1: Hexamethylene bis-acetamide inducible 1; HEXIM2: Hexamthylene bis-acetamide inducible 2; LMAN1L: Lectin, mannose-binding, 1 like; MTHFR: Methylenetetrahydrofolate reductase (NAD(P)H); NPPA: Natriuretic peptide A; NPPB: Natriuretic peptide B; NT5C2: 5'-nucleotidase, cytosolic II; PHB: Prohibitin; PLCD3: Phospholipase C, Δ 3; PLEKHA7: Pleckstrin homology domain containing, family A member 7; PRDM8: PR domain containing 8; RHOBTB1: Rho-related BTB domain containing 1; RTKN2: Rhotekin 2; SH2B3: SH2B adaptor protein 3; STK39: Serine threonine kinase 39; TBX3: T-box 3; TBX5: T-box 5; TMEM26: Transmembrane protein 26; ULK3: Unc-51-like kinase 3 (C. elegans); ULK4: Unc-51-like kinase 4 (C. elegans); UMOD: Uromodulin, ZNF652: Zinc finger protein 652; SNP: Single nucleotide polymorphisms; OR: Odds ratio.