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

Table 3 Five most significant association results using FBAT and GEE within phenotype clusters for each of five multivariable-adjusted subclinical atherosclerosis measures

Phenotype group	Rank GEE/FBAT	SNP	Chr	Physical location	%Phenotypes P < 0.01 for GEE & FBAT	GEE P-value geometric mean	MAF	Gene position	Gene symbol
Ankle brachial index	1	rs7989017	13	25,164,878	100	4.7 × 10^-3	0.22	IN	ATP8A2
	2	rs7546903	1	6,870,538	75	1.7 × 10^-3	0.27	IN	CAMTA1
	3	rs6135095	20	1,422,405	75	3.0 × 10^-3	0.14	NEAR	SIRPB2
	4	rs1875517	3	118,790,257	75	3.4 × 10^-3	0.44	OUT
	5	rs6507763	18	43,310,669	75	3.5 × 10^-3	0.14	OUT
Common carotid artery IMT	1	rs1039610	18	74,049,795	100	4.9 × 10^-5	0.32	OUT
	2	rs1587893	18	74,039,913	100	5.8 × 10^-5	0.31	OUT
	3	rs28207	5	13,267,852	100	8.1 × 10^-5	0.37	OUT
	4	rs4814615	20	17,305,573	100	1.3 × 10^-4	0.16	IN	PCSK2
	5	rs2470209	17	28,263,442	100	1.9 × 10^-4	0.39	NEAR	MYO1D
Internal carotid artery IMT	1	rs933890	12	106,941,389	100	6.6 × 10^-4	0.22	OUT
	2	rs8075776	17	36,408,189	100	9.8 × 10^-4	0.16	NEAR	KRTAP1-1, KRTAP1-3
	3	rs252984	5	106,780,236	100	1.0 × 10^-3	0.16	IN	EFNA5
	4	rs10490889	3	6,257,028	100	1.6 × 10^-3	0.36	OUT
	5	rs10516308	4	16,780,451	100	3.3 × 10^-3	0.41	OUT
Coronary artery calcification	1	rs10483853	14	72,826,052	100	9.8 × 10^-6	0.19	IN	NUMB
	2	rs10507130	12	100,256,422	100	1.3 × 10^-5	0.22	IN	DRIM
	3	rs9321354	6	132,946,880	100	3.4 × 10^-5	0.12	NEAR	TAAR8, TAAR6, TAAR5
	4	rs220457	17	27,126,748	100	3.8 × 10^-4	0.25	OUT
	5	rs10505182	8	113,337,274	100	5.2 × 10^-4	0.23	IN	CSMD3

Abbreviations: SNP = single nucleotide polymorphism; Chr = chromosome; GEE = generalized estimating equations; FBAT = family based association testing; IMT = intimal medial thickness; MAF = minor allele frequency.
Column Definitions: For each Phenotype Group (Table column one), a cluster analysis is conducted for several phenotype variables defined in Table 1. For “Ankle brachial index,” GEE and FBAT results were evaluated for RANKLEBI6, RANKLEBI6MV, RANKLEBI7, and RANKLEBI7MV; for “Common carotid artery IMT,” RNKCAROTCCAMAXAS6, RNKCAROTCCAMAXMV6, RNKCAROTCCAMEANAS6, and RNKCAROTCCAMEANMV6; for “Internal carotid artery IMT,” RNKCAROTICAMAXAS6, RNKCAROTICAMAXMV6, RNKCAROTICAMEANAS6, and RNKCAROTICAMEANMV6; and for “Coronary artery calcification,” RESMDCTCACMAXMV7 and RESMDCTCACMV7. The percent of phenotypes in the cluster analysis for which there was a p < 0.01 by both GEE and FBAT analyses is shown in Table column five. The geometric mean p-value is shown in Table column six for GEE associations for all phenotypes in the cluster analyses. For proximity to known genes (Gene position, Table column eight), “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.

ISSN: 1471-2350