Table 3 Mendelian Randomization of CHIP-associated CpGs and CVD-related Outcomes

From: Epigenome-wide DNA methylation association study of CHIP provides insight into perturbed gene regulation

CHIP Category

Exposure

Outcome

β

SE

P-value

FDR

Nearby Gene

Association with CHIP*

DNMT3A

cg11250194

LDL cholesterol

−0.89

0.074

2.0E-33

1.1E-28

FADS2

-

TET2

cg20305489

Diastolic blood pressure

10

0.89

1.7E-31

6.7E-27

SEPT9

+

TET2

cg20305489

Systolic blood pressure

16

1.5

3.6E-26

1.3E-21

SEPT9

+

Any CHIP/DNMT3A/ASXL1

cg00776080

Diastolic blood pressure

−28

2.7

2.6E-24

7.9E-20

TENC1

-

Any CHIP/ASXL1

cg11879188

Diastolic blood pressure

2.7

0.27

1.9E-23

4.7E-19

ABO

-

Any CHIP

cg24530246

HDL cholesterol

0.46

0.047

1.2E-22

2.7E-18

 

-

DNMT3A

cg11250194

HDL cholesterol

−1.5

0.16

1.3E-22

2.7E-18

FADS2

-

DNMT3A

cg11250194

Triglycerides

1.4

0.14

1.8E-22

3.6E-18

FADS2

-

DNMT3A

cg16517298

HDL cholesterol

0.56

0.062

1.1E-19

1.6E-15

GALNT2

-

Any CHIP/DNMT3A

cg17892169

Diastolic blood pressure

8.9

0.99

2.2E-19

3.2E-15

TNFSF12

-

TET2

cg01687878

Diastolic blood pressure

−6.7

0.75

3.8E-19

5.2E-15

 

+

TET2

cg10632966

Systolic blood pressure

25

2.8

3.3E-18

3.8E-14

 

+

Any CHIP/ASXL1

cg11879188

Myocardial infarction

−0.99

0.11

4.8E-18

5.3E-14

ABO

-

DNMT3A

cg16517298

Triglycerides

−0.55

0.064

8.0E-18

7.9E-14

GALNT2

-

Any CHIP

cg00417151

HDL cholesterol

0.85

0.10

2.7E-17

2.6E-13

RRBP1

-

TET2

cg16060189

Type 2 diabetes

2.4

0.29

1.1E-16

9.4E-13

 

+

TET2

cg14016363

Diastolic blood pressure

−21

2.5

1.3E-16

1.0E-12

 

+

Any CHIP

cg00526336

Triglycerides

−2.1

0.28

2.5E-14

1.4E-10

GALNT2

-

Any CHIP/DNMT3A

cg06346307

Systolic blood pressure

−11

1.5

2.7E-14

1.5E-10

COMT

-

Any CHIP

cg19758448

HDL cholesterol

−0.54

0.073

1.0E-13

5.5E-10

PGAP3

-

  1. The effect size (β), standard error (SE), and P-values were derived from two-sample Mendelian randomization (MR) tests. Two-sided tests were used for all analyses. FDR values were calculated using the Benjamini-Hochberg FDR method.
  2. *“Association with CHIP”: “+” or “-” represent the directions of effect for any CHIP, DNMT3A, TET2, or ASXL1 CHIP in meta-EWAS.
  3. CHIP Clonal Hematopoiesis of Indeterminate Potential.
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