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Table 2 Top genetic associations with biomarkers based on the lowest p value for GEE test (2a), FBAT (2b), and Linkage (2c)

From: Genome-wide association with select biomarker traits in the Framingham Heart Study

2a. Top 25 associations with biomarkers based on the lowest p value of the GEE test

Trait

SNP rs ID*

Chr

Physical location (bp)

GEE P-value

FBAT P-value

IN/NEAR gene

 

Monocyte chemoattractant protein-1

rs2494250

1

156091324

1.0*10 -14

3.5*10-8

FCER1A, OR10J3

 

Monocyte chemoattractant protein-1

rs4128725

1

156219032

3.7*10 -12

3.3*10-8

OR10J1

 

C-reactive protein average exams 2,6,7

rs2794520

1

156491889

2.8*10 -8

4.3*10-5

CRP

 

C-reactive protein average exams 2,6,7

rs2808629

1

156489869

3.2*10 -8

4.8*10-5

CRP

 

C-reactive protein exam 6

rs2794520

1

156491889

1.3*10 -7

3.9*10-4

CRP

 

C-reactive protein exam 6

rs2808629

1

156489869

1.4*10 -7

4.3*10-4

CRP

 

Tumor necrosis factor alpha

rs7552393

1

83966572

5.1*10 -7

0.63

  

C-reactive protein exam 6

rs746961

19

35791730

7.5*10 -7

0.03

ZNF536

 

Bilirubin

rs17532515

4

141745043

1.0*10 -6

9.2*10-6

CLGN, ELMOD2

 

Alanine aminotransferase

rs1998303

9

82644535

1.1*10 -6

0.005

  

Monocyte chemoattractant protein-1

rs10489849

1

156009838

1.1*10 -6

0.10

IGSF4B

 

Alkaline phosphatase

rs10518765

15

52467924

1.1*10 -6

1.7*10-4

  

Vitamin K plasma phylloquinone

rs2387326

10

129823446

1.1*10 -6

0.02

PTPRE, MKI67

 

C-reactive protein average exams 2,6,7

rs1119582

5

125270919

1.2*10 -6

4.2*10-4

  

Vitamin D plasma 25(OH)-D

rs10485165

6

89169536

1.4*10 -6

0.003

  

Atrial natriuretic peptide exam 6

rs1417352

6

107005919

1.8*10 -6

0.009

  

C-reactive protein exam 2

rs583012

10

54964880

1.9*10 -6

0.09

  

Atrial natriuretic peptide exam 6

rs1486139

7

46048968

2.0*10 -6

0.04

  

Atrial natriuretic peptide exam 6

rs1486140

7

46048877

2.2*10 -6

0.06

  

Alanine aminotransferase exam 2

rs10492681

13

39705483

2.2*10 -6

9.9*10-5

  

Vitamin D plasma 25(OH)-D

rs10507577

13

52866092

2.6*10 -6

0.004

  

Atrial natriuretic peptide exam 6

rs1079596

11

112801829

2.6*10 -6

0.03

DRD2

 

Monocyte chemoattractant protein-1

rs1474747

1

155961586

2.8*10 -6

8.7*10-4

IGSF4B

 

CD40 Ligand serum

rs7778619

7

9923216

3.0*10 -6

0.19

  

CD40 Ligand serum

rs8005745

14

76473583

3.5*10 -6

0.01

  

2b. Top 25 associations with biomarkers based on the lowest p value of the FBAT test

Trait

SNP rs ID*

Chr

Physical location (bp)

GEE P-value

FBAT P-value

IN/NEAR gene

 

Monocyte chemoattractant protein-1

rs4128725

1

156219032

3.7*10-12

3.3*10 -8

OR10J1

 

Monocyte chemoattractant protein-1

rs2494250

1

156091324

1.0*10-14

3.5*10 -8

FCER1A, OR10J3

 

B-type natriuretic peptide

rs437021

1

61450291

1.5*10-4

1.0*10 -6

NFIA

 

Vitamin K % undercarboxylated osteocalcin

rs2052028

7

15789103

5.2*10-6

1.1*10 -6

  

CD40 Ligand plasma

rs2372184

3

65673194

0.003

2.5*10 -6

MAGI1

 

Urinary isoprostanes/creatinine

rs717145

20

15826091

0.003

5.0*10 -6

C20orf133

 

CD40 Ligand serum

rs4664604

2

153398916

0.01

8.4*10 -6

ARL6IP6

 

CD40 Ligand serum

rs9288125

2

153348619

0.01

9.1*10 -6

FMNL2, ARL6IP6

 

C-reactive protein exam 7

rs1363258

5

103297593

0.02

9.2*10 -6

  

Bilirubin

rs17532515

4

141745043

1.0*10-6

9.2*10 -6

CLGN, ELMOD2

 

Osteoprotegerin

rs496269

6

79457094

0.03

9.4*10 -6

  

C-reactive protein average 2,6,7

rs1363258

5

103297593

0.009

1.3*10 -5

  

CD40 Ligand serum

rs303939

13

71269472

0.008

1.3*10 -5

DACH1

 

Myeloperoxidase

rs10501981

11

100880825

1.1*10-5

1.4*10 -5

TRPC6

 

Urinary isoprostanes/creatinine

rs1461549

14

24782140

0.26

1.5*10 -5

  

Tumor necrosis factor alpha

rs2353803

7

11060282

0.03

1.5*10 -5

  

Intercellular adhesion molecule-1

rs3849944

9

27550594

5.3*10-6

1.5*10 -5

C9orf72

 

CD40 Ligand serum

rs1986743

2

153412407

0.01

1.6*10 -5

ARL6IP6

 

Gamma-glutamyl transferase

rs962976

12

67006894

0.002

1.6*10 -5

MDM1

 

C-reactive protein average 2,6,7

rs2421608

2

117013763

0.02

1.8*10 -5

  

C-reactive protein exam 2

rs642245

11

86067184

0.03

1.9*10 -5

ME3

 

Tumor necrosis factor receptor-2

rs248328

5

179309691

0.59

1.9*10 -5

TBC1D9B, RNF130

 

C-reactive protein exam 7

rs2390582

1

90655928

0.07

2.0*10 -5

  

Osteoprotegerin

rs9352609

6

79442188

0.04

2.0*10 -5

  

Intercellular adhesion molecule-1

rs744511

14

39166736

3.2*10-4

2.1*10 -5

  

2c. Magnitude and Location of Peak LOD scores > 2.5 for regions in the Biomarker Phenotype Group

Trait

Exam

Chr

Physical location (bp)

Maximum LOD

LOD-1.5 Interval

LOD+1.5 Interval

Maximum LOD WIN*

Monocyte chemoattractant protein-1

7

1

159093573

4.96

154908901

159751221

4.38

Monocyte chemoattractant protein-1

7

10

129553148

4.03

128294406

130084334

3.23

C-reactive protein

5

1

154745847

3.53

153213133

156567571

3.28

Monocyte chemoattractant protein-1

7

17

13630703

3.33

10874193

16776778

2.54

Intercellular adhesion molecule-1

7

1

203535232

2.95

202207846

215367881

2.93

Monocyte chemoattractant protein-1

7

7

92544810

2.94

88727093

105546050

2.01

Tumor necrosis factor receptor 2

7

1

54001041

2.92

43070922

60590679

2.95

Gamma-glutamyl transferase

2

3

26424584

2.89

24621158

27418642

2.96

B-type natriuretic peptide

6

12

4140574

2.77

132045

8137669

No outliers

Gamma-glutamyl transferase

2

10

129553148

2.67

120112006

132560638

2.79

Vitamin D plasma 25(OH)-D

6/7

8

140624328

2.67

138952328

146039126

2.68

B-type natriuretic peptide

6

19

34016706

2.59

13425865

43186344

No outliers

Myeloperoxidase

7

19

11295505

2.56

3026853

16489850

2.56

Alkaline phosphatase

2

6

170538204

WIN

162441307

170788550

2.55

Osteoprotegerin

7

13

75274475

2.52

71928655

81228082

2.95

  1. bp = base pair; Chr = chromosome; WIN = Winsorized.
  2. dbSNP positions are from NCBI Build 35 (hg17);
  3. LD between rs2494250 and rs4128725 (top MCP1 SNPs): D' = 0.724 and r squared = 0.196.
  4. LD between rs2794520 and rs2808629 (top CRP SNPs): D' = 1.0 and r squared = 1.0.
  5. *Winsorized LOD scores were run for this manuscript, and are not displayed on the web.
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BMC Medical Genetics

ISSN: 1471-2350

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