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Table 4 SNPs in or near previously reported candidate genes for coronary heart disease or subclinical atherosclerosis for multivariable-adjusted SCA phenotypes: SNPs with p < 0.01 in GEE or FBAT analyses, or p < 0.05 in both GEE and FBAT analyses.

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

Chr

Gene

N SNPs within 60 kb

SNP from Affy 100K Array

MAF

Physical Location

Phenotype

Lowest P-value

       

GEE

FBAT

3

CCR5

1/6

rs3762823

0.25

46,371,620

Common carotid artery IMT

0.02

0.04

      

Common carotid artery IMT

0.05

0.04

4

FGB

1/7

rs871540

0.22

155,766,635

Abdominal aortic calcification

0.11

3.0 × 10-3

6

ESR1

8/18

rs3866461

0.12

152,238,835

Coronary artery calcification

5.4 × 10-3

0.11

      

Coronary artery calcification

3.4 × 10-3

0.12

   

rs3853250

0.45

152,252,014

Ankle brachial index

0.05

0.04

   

rs3853251

0.34

152,252,870

Ankle brachial index

0.03

0.02

   

rs722208

0.27

152,414,999

Coronary artery calcification

0.54

5.7 × 10-3

      

Coronary artery calcification

0.57

5.0 × 10-3

   

rs3798573

0.11

152,481,476

Internal carotid artery IMT

6.4 × 10-3

0.78

   

rs3778099

0.10

152,510,689

Common carotid artery IMT

0.82

6.9 × 10-3

   

rs2813563

0.19

152,538,601

Abdominal aortic calcification

0.02

0.03

   

rs725467

0.19

152,539,833

Abdominal aortic calcification

0.02

0.03

7

IL6

2/9

rs1581498

0.45

22,681,483

Coronary artery calcification

0.16

7.7 × 10-3

      

Coronary artery calcification

0.04

3.3 × 10-3

   

rs10240716

0.27

22,765,225

Ankle brachial index

0.01

0.04

7

NOS3

2/3

rs768403

0.38

150,297,894

Abdominal aortic calcification

2.0 × 10-3

0.02

   

rs7812088

0.12

150,357,477

Internal carotid artery IMT

0.05

5.5 × 10-3

      

Internal carotid artery IMT

0.05

0.01

8

TNFRSF11

1/9

rs10505346

0.21

120,033,024

Ankle brachial index

0.04

0.05

11

ADM

3/5

rs10500724

0.44

10,258,592

Ankle brachial index

2.0 × 10-4

5.0 × 10-4

   

rs4444073

0.47

10,288,240

Ankle brachial index

3.3 × 10-3

5.0 × 10-4

   

rs4444073

  

Ankle brachial index

0.01

0.04

11

CD44

10/24

rs1365057

0.22

35,066,251

Coronary artery calcification

0.05

8.9 × 10-3

      

Coronary artery calcification

0.05

7.7 × 10-3

   

rs353589

0.21

35,077,802

Ankle brachial index

9.0 × 10-3

0.08

      

Abdominal aortic calcification

7.4 × 10-3

0.10

   

rs353639

0.21

35,140,940

Ankle brachial index

8.3 × 10-3

0.03

      

Ankle brachial index

3.1 × 10-3

0.04

   

rs353638

0.21

35,141,103

Ankle brachial index

5.6 × 10-3

0.05

      

Ankle brachial index

4.2 × 10-3

0.06

   

rs353636

0.21

35,141,306

Ankle brachial index

7.6 × 10-3

0.05

      

Ankle brachial index

4.2 × 10-3

0.06

   

rs353635

0.46

35,141,399

Ankle brachial index

0.09

4.6 × 10-3

   

rs353631

0.20

35,144,144

Ankle brachial index

4.8 × 10-3

0.06

      

Ankle brachial index

4.5 × 10-3

0.15

   

rs1467558

0.21

35,186,249

Coronary artery calcification

0.03

0.02

      

Coronary artery calcification

0.03

0.02

   

rs10488813

0.13

35,225,530

Abdominal aortic calcification

8.8 × 10-3

0.48

   

rs7115246

0.46

35,243,054

Ankle brachial index

7.1 × 10-3

9.4 × 10-3

17

CCL2

1/7

rs1024612

0.41

29,573,469

Abdominal aortic calcification

3.6 × 10-3

0.22

  1. Abbreviations: SNP = single nucleotide polymorphism; Chr = chromosome; GEE = generalized estimating equations; FBAT = family based association testing; IMT = intimal medial thickness; MAF = minor allele frequency.
  2. Of 37 candidate genes considered, there were 28 genes covered by the 100K array and meeting exclusion criteria, of which nine genes had a significantly associated SNP(s) with either p < 0.01 for GEE, p < 0.01 for FBAT, or p < 0.05 for both GEE and FBAT. Genes without significant associations meeting these criteria included: F5, MTHFR, REN, APOB, CX3CR1, GATA2, EDN1, CTGF, VEGF, PON1, MMP3, SCARB1, ALOX5AP, CETP, ITGB3, NOS2A, APO3, and MMP9. However, it should be noted that 100K SNP coverage of any given gene region may be insufficient to exclude real associations. Better coverage may be afforded by newer, more dense SNP arrays. Only SNPs within the introns or exons of the candidate gene or no greater than 60 kb away from the candidate gene were considered for Table 4 (denominator of Column 3).
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BMC Medical Genetics

ISSN: 1471-2350

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