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.