Table 1 Estimates of the effect of genetically predicted liver enzymes ALT, ALP and GGT (per 100% change in concentration)18 on coronary artery disease (CAD)/myocardial infarction (MI)12,14,22 and type 2 diabetes mellitus (T2DM)15 using Mendelian randomization with different methodological approaches with and without potentially pleiotropic SNPs.

From: Liver Enzymes and Risk of Ischemic Heart Disease and Type 2 Diabetes Mellitus: A Mendelian Randomization Study

Outcome

data source

Liver Enzyme

All SNPs

Excluding potentially pleiotropic SNPs‡

SNPs

Method

OR

95% CI

MR-Egger§

SNPs

Method

OR

95% CI

MR-Egger§

Intercept

Intercept p value

Intercept

Intercept p value

CAD/MI

CARDIoGRAMplusC4D

ALT

4

IVW

0.89

0.54 to 1.46

0.07

0.12

3

IVW

0.79

0.48 to 1.31

0.03

0.47

CARDIoGRAMplusC4D 1000 genomes

  

IVW

0.79

0.58 to 1.08

0.04

0.28

 

IVW

0.74

0.54 to 1.01

0.004

0.836

CARDIoGRAMplusC4D

  

MR-Egger

0.18

0.01 to 5.75

—

—

 

MR-Egger

0.43

0.13 to 1.43

—

—

CARDIoGRAMplusC4D 1000 genomes

  

MR-Egger

0.33

0.01 to 9.62

—

—

 

MR-Egger

0.68

0.10 to 4.73

—

—

CARDIoGRAMplusC4D

ALP

14

IVW

0.72

0.57 to 0.91

0.03

0.06

9

IVW

1.44

0.95 to 2.17

−0.03

0.16

CARDIoGRAMplusC4D 1000 genomes

  

IVW

0.61

0.50 to 0.74

0.02

0.08

 

IVW

0.86

0.64 to 1.16

−0.01

0.72

CARDIoGRAMplusC4D

  

MR-Egger

0.38

0.17 to 0.86

—

—

 

WM

1.54

0.91 to 2.63

—

—

CARDIoGRAMplusC4D 1000 genomes

  

WM

0.46

0.35 to 0.60

—

—

 

WM

0.94

0.60 to 1.48

—

—

CARDIoGRAMplusC4D

GGT

26

IVW

1.11

0.97 to 1.27

0.004

0.662

23

IVW

1.12

0.97 to 1.29

0.001

0.91

CARDIoGRAMplusC4D 1000 genomes

  

IVW

1.01

0.92 to 1.10

0.01

0.34

 

IVW

1.08

0.97 to 1.19

0.01

0.55

CARDIoGRAMplusC4D

  

WM

1.16

0.94 to 1.42

—

—

 

WM

1.16

0.94 to 1.44

—

—

CARDIoGRAMplusC4D 1000 genomes

  

WM

1.03

0.89 to 1.19

—

—

 

WM

1.05

0.91 to 1.23

—

—

Diabetes

DIAGRAM

ALT

4

IVW

2.68

1.48 to 4.86

−0.01

0.70

3

IVW

2.99

1.62 to 5.52

0.02

0.64

  

MR-Egger

3.54

0.17 to 73.79

—

—

 

MR-Egger

1.99

0.16 to 24.36

—

—

DIAGRAM

ALP

14

IVW

0.91

0.70 to 1.18

0.01

0.28

13

IVW

0.92

0.71 to 1.19

0.01

0.24

  

MR-Egger

0.71

0.35 to 1.45

—

—

 

MR-Egger

0.68

0.32 to 1.44

—

—

DIAGRAM

GGT

26

IVW

0.83

0.71 to 0.97

−0.02

0.09

24

IVW

0.88

0.75 to 1.04

−0.01

0.33

  

WM

0.82

0.62 to 1.10

—

—

 

WM

0.91

0.68 to 1.21

—

—

  1. IVW: Inverse Variance Weighted, WM: Weighted Median.
  2. ‡CAD/MI related SNPs excluded for ALT: rs2954021 (TRIB1), excluded for ALP: rs174601 (C11orf10, FADS1, FADS2), rs314253 (ASGR1, DLG4), rs2954021 (TRIB1), rs579459 (ABO) and rs6984305 (PPP1R3B), excluded for GGT: rs516246 (FUT2), rs7310409 (HNF1A) and rs1260326 (C2orf16, GCKR).
  3. Diabetes related SNPs excluded for GGT: rs516246 (FUT2) and rs1260326 (C2orf16, GCKR); rs2954021 (TRIB1) excluded for ALT and ALP.
  4. §The intercept can be interpreted as an estimate of the average pleiotropic effect across the genetic variants where a corresponding p-value of <0.05 indicates the presence of directional pleiotropy across the genetic variants included in the analyses.
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