Genome-wide association study for subclinical atherosclerosis in major arterial territories in the NHLBI's Framingham Heart Study

O'Donnell, Christopher J; Cupples, L Adrienne; D'Agostino, Ralph B; Fox, Caroline S; Hoffmann, Udo; Hwang, Shih-Jen; Ingellson, Erik; Liu, Chunyu; Murabito, Joanne M; Polak, Joseph F; Wolf, Philip A; Demissie, Serkalem

doi:10.1186/1471-2350-8-S1-S4

Table 2 25 Most significant results for multivariable-adjusted subclinical atherosclerosis measures in multiple arterial territories by GEE (2a), FBAT (2b) and linkage (2c) analyses

From: Genome-wide association study for subclinical atherosclerosis in major arterial territories in the NHLBI's Framingham Heart Study

2a. Most significant results for GEE analyses for multivariable-adjusted subclinical atherosclerosis measures
GEE rank	Phenotype	SNP	Chr	Physical location	GEE P-value	FBAT P-value	Gene position	Gene symbol
1	Internal carotid artery IMT	rs1376877	2	204,097,596	3.8 × 10^-7	0.15	IN	ABI2
3	Coronary artery calcification	rs2390582	1	90,655,928	1.4 × 10^-6	0.34	OUT
4	Abdominal aortic calcification	rs3849150	10	49,779,229	1.6 × 10^-6	4.0 × 10^-3	NEAR	LRRC18
6	Ankle brachial index	rs2896103	5	13,817,419	4.5 × 10^-6	0.01	IN	DNAH5
7	Coronary artery calcification	rs10483853	14	72,826,052	6.1 × 10^-6	1.7 × 10^-3	IN	NUMB
8	Common carotid artery IMT	rs1400544	1	186,593,061	6.2 × 10^-6	4.7 × 10^-4	OUT
9	Ankle brachial index	rs7715811	5	13,822,974	6.4 × 10^-6	0.02	IN	DNAH5
10	Coronary artery calcification	rs10507130	12	100,256,422	6.7 × 10^-6	1.6 × 10^-3	IN	DRIM
11	Ankle brachial index	rs1320267	4	127,290,897	6.9 × 10^-6	0.03	OUT
13	Ankle brachial index	rs1350445	11	91,591,802	8.5 × 10^-6	0.07	OUT
14	Ankle brachial index	rs1502050	5	13,832,743	8.7 × 10^-6	0.02	IN	DNAH5
15	Coronary artery calcification	rs10519394	4	137,962,214	1.1 × 10^-5	0.03	OUT
16	Internal carotid artery IMT	rs683366	18	52,370,975	1.2 × 10^-5	0.01	NEAR	TXNL1
19	Abdominal aortic calcification	rs2850711	18	59,938,018	1.5 × 10^-5	0.05	IN	C18orf20
20	Internal carotid artery IMT	rs601746	10	96,932,273	1.6 × 10^-5	0.22	NEAR	C10orf129
21	Ankle brachial index	rs1905155	5	113,301,097	1.6 × 10^-5	5.1 × 10^-3	OUT
22	Ankle brachial index	rs10501784	11	91,592,192	1.6 × 10^-5	0.30	OUT
23	Ankle brachial index	rs10493529	1	74,335,469	1.9 × 10^-5	0.098	NEAR	LRRC44, FPGT
24	Common carotid artery IMT	rs28207	5	13,267,852	1.9 × 10^-5	2.1 × 10^-4	OUT
25	Abdominal aortic calcification	rs8094641	18	59,873,880	2.0 × 10^-5	0.04	NEAR	C18orf20
26	Ankle brachial index	rs2949535	18	26,111,783	2.0 × 10^-5	7.5 × 10^-4	OUT
27	Coronary artery calcification	rs2270861	12	100,238,849	2.0 × 10^-5	6.8 × 10^-3	IN	DRIM
28	Common carotid artery IMT	rs853406	6	4,002,159	2.2 × 10^-5	1.9 × 10^-3	IN	PRPF4B
29	Common carotid artery IMT	rs853407	6	4,002,232	2.2 × 10^-5	2.5 × 10^-3	IN	PRPF4B
30	Common carotid artery IMT	rs1581413	3	158,532,867	2.2 × 10^-5	1.8 × 10^-3	IN	VEPH1
2b. Most significant results for FBAT analyses for multivariable-adjusted subclinical atherosclerosis measures
FBAT rank	Phenotype	SNP	Chr	Physical location	GEE P-value	FBAT P-value	Gene position	Gene symbol
1	Common carotid artery IMT	rs4814615	20	17,305,573	4.9 × 10^-5	3.4 × 10^-6	IN	PCSK2
2	Common carotid artery IMT	rs6053733	20	5,763,074	7.2 × 10^-3	3.7 × 10^-6	IN	C20orf196
3	Ankle brachial index	rs10499903	7	90,504,268	1.9 × 10^-3	4.1 × 10^-6	NEAR	PFTK1, FZD1
4	Ankle brachial index	rs9302997	17	71,723,439	4.8 × 10^-3	5.1 × 10^-6	IN	RNF157
5	Ankle brachial index	rs590183	4	23,733,535	0.01	8.6 × 10^-6	OUT
7	Ankle brachial index	rs6832344	4	23,733,805	9.9 × 10^-3	1.0 × 10^-5	OUT
8	Abdominal aortic calcification	rs1023568	2	191,340,948	0.09	1.2 × 10^-5	IN	NAB1
9	Common carotid artery IMT	rs2214959	12	124,674,521	0.01	1.5 × 10^-5	NEAR	TMEM132B
10	Ankle brachial index	rs9285151	13	42,712,236	0.06	1.7 × 10^-5	IN	ENOX1
11	Ankle brachial index	rs1381632	4	88,926,163	0.36	1.8 × 10^-5	NEAR	DMP1
12	Coronary artery calcification	rs4461066	16	51,469,110	8.7 × 10^-3	3.1 × 10^-5	OUT
15	Coronary artery calcification	rs367421	20	15,202,689	2.5 × 10^-3	3.6 × 10^-5	IN	C20orf133
16	Internal carotid artery IMT	rs9323431	14	62,638,241	0.24	3.6 × 10^-5	IN	KCNH5
17	Common carotid artery IMT	rs1997463	3	54,782,280	0.01	3.8 × 10^-5	IN	CACNA2D3
19	Common carotid artery IMT	rs304409	18	1,096,342	1.8 × 10^-4	4.6 × 10^-5	OUT
21	Internal carotid artery IMT	rs1349008	3	76,804,103	0.23	4.9 × 10^-5	OUT
22	Ankle brachial index	rs2251671	8	40,501,973	1.3 × 10^-4	4.9 × 10^-5	NEAR	ZMAT4
23	Abdominal aortic calcification	rs243030	2	60,518,222	3.1 × 10^-5	5.6 × 10^-5	OUT
24	Abdominal aortic calcification	rs321967	7	77,959,200	4.7 × 10^-4	6.0 × 10^-5	IN	MAGI2
25	Ankle brachial index	rs6569792	6	132,736,444	0.56	6.4 × 10^-5	IN	MOXD1
26	Abdominal aortic calcification	rs4985741	17	17,028,605	7.2 × 10^-3	6.6 × 10^-5	IN	MRIP
27	Ankle brachial index	rs7995026	13	42,751,550	6.9 × 10^-4	6.9 × 10^-5	IN	ENOX1
28	Coronary artery calcification	rs10520541	4	184,055,754	0.08	7.0 × 10^-5	IN	AK001336
29	Internal carotid artery IMT	rs2113945	15	29,111,823	0.09	7.2 × 10^-5	IN	TRPM1
30	Common carotid artery IMT	rs6944400	7	131,389,740	0.12	8.2 × 10^-5	OUT
2c. Genomic regions with LOD > 2.0 for linkage analyses for multivariable-adjusted subclinical atherosclerosis measures
Rank	Phenotype	Marker	Chr	Physical location	LOD score 1.5 interval bounds		Maximum LOD
1	Internal carotid artery IMT	ATA29A06	12	128,922,618	127,583,749	129,277,512	5.05
2	Internal carotid artery IMT	rs959987	12	127,817,680	126,600,362	129,277,512	4.78
3	Internal carotid artery IMT	rs1180937	1	54,903,665	45,417,474	56,950,040	4.23
8	Abdominal aortic calcification	rs17030524	12	99,640,364	97,320,770	102,339,523	3.51
6	Coronary artery calcification	SNP_A-1679277	6	149,300,408	136,476,887	154,228,170	2.81
7	Ankle brachial index	rs394884	2	151,954,268	142,801,622	168,477,710	2.73
9	Internal carotid artery IMT	rs300574	4	124,681,343	118,755,997	131,657,093	2.49
10	Internal carotid artery IMT	rs714647	15	99,870,157	96,719,695	100,152,332	2.49
12	Coronary artery calcification	rs1106679	14	102,555,405	91,636,556	106,312,036	2.33
13	Abdominal aortic calcification	rs1454183	2	13,935,308	3,238,478	20,119,479	2.31
15	Coronary artery calcification	rs7000744	8	140,003,669	136,360,837	146,039,126	2.23
16	Ankle brachial index	rs10483084	21	42,268,393	40,113,290	45,025,009	2.12
17	Internal carotid artery IMT	rs1948685	5	21,064,843	10,288,046	31,560,322	2.11
19	Internal carotid artery IMT	rs10832008	11	13,232,905	6,384,682	19,637,706	2.09

Abbreviations: SNP = single nucleotide polymorphism; Chr = chromosome; GEE = generalized estimating equations; FBAT = family based association testing; LOD = logarithm of the odds; IMT = intimal medial thickness;. Gaps appear in the rank order for markers that appear more than once. In the column entitled “Phenotype”, 'internal carotid artery IMT' denotes either mean or maximum internal carotid IMT, 'common carotid artery IMT' denotes either mean or maximum common carotid IMT, 'coronary artery calcification' denotes either mean CAC or max CAC, and 'ankle brachial index' denotes and ankle brachial index from either examination cycle 6 or cycle 7. For proximity to known genes (Table columns nine and ten), “IN” refers to a SNP within a protein-coding gene intron or exon, “OUT” refers to a SNP greater than 60 kb away from a protein-coding gene gene, and “NEAR” refer to a SNP within 60 kb of a protein-coding gene.

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