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Table 3 Mendelian randomization analysis results of causal CpG sites for metabolic traits, selected among the top ten EWAS most significant hits

From: DNA methylation may partly explain psychotropic drug-induced metabolic side effects: results from a prospective 1-month observational study

Exposure

MR resultsa

EWAS resultsb

CHR

CpG position in Genome Build 37

Reference genec

Location of CpG related to genec

Relation to CpG Islandd

Outcome

N SNPs

Beta

SE

p-value

CpG data

Beta

SE

p-value

cg11622362

Glucose

2

0.019

0.005

0.0001

T0

− 1.05

0.22

2.96 × 10–5

11

34,938,112

APIP*

TSS200

Island

cg09137125

Glucose

2

− 0.003

0.007

0.63

T0

− 0.93

0.19

3.51 × 10–5

10

7,486,981

   

cg26295559

Glucose

4

0.003

0.004

0.55

T0-T1

− 2.40

0.46

1.02 × 10–5

7

158,550,318

ESYT2

Body

 

cg09694300

HDL

2

− 0.025

0.019

0.18

T0

− 1.25

0.28

5.58 × 10–5

3

159,429,667

SCHIP1

Body

 

cg23700124

LDL

2

0.001

0.005

0.86

T0

− 0.69

0.14

1.15 × 10–5

4

123,843,736

SPATA5*

TSS1500

Island

cg03803210

TG

3

0.001

0.005

0.87

T0-T1

1.93

0.34

8.93 × 10–7

8

17,438,816

PDGFRL

Body

S_Shelf

cg08387293

TG

2

0.002

0.008

0.82

T0-T1

− 3.22

0.58

1.13 × 10–6

1

984,383

AGRN

Body

Island

  1. CHR chromosome, EWAS epigenome-wide association study, HDL high density lipoprotein cholesterol, LDL low-density lipoprotein cholesterol, MR Mendelian randomization, SE standard error, SNPs single nucleotide polymorphisms, TG triglycerides
  2. aTwo-sample MR analyses using the inverse-variance weighted method were performed. Summary statistics for instrument-exposure association (n = 3,841) were retrieved from Bonder et al. [40], while instrument-outcome association statistics were derived from GWAS performed in the UKBiobank (http://www.nealelab.is/uk-biobank; n = 314′916 for glucose, n = 315′133 for HDL, n = 343′621 for LDL, n = 343,992 for TG). Significant p-values (< 0.05) are indicated in bold
  3. bThe results of the EWAS using methylation M-values are displayed. For the first line, the magnitude of the effect in β-value is to be interpreted as follows: a difference of 1.4% in baseline methylation level (corresponding to baseline methylation IQR in PsyMetab sample) is associated with a 0.39 mM (SE = 0.07) smaller glucose increase. No result reached statistical significance
  4. cReference genes for the methylation sites, and gene regions where the CpGs are located according to the UCSC database. Empty fields indicate an intergenic location
  5. *Specifies there exists > 1 gene or gene transcript at this location. TSS200 = 0–200 bases upstream of the transcriptional start site (TSS); TSS1500 = 200–1500 bases upstream of the TSS; Body = between the ATG and stop codon, irrespective of the presence of introns, exons, TSS, or promoters
  6. dThe relation to a putative nearby CpG island, according to the UCSC database, is given. S_Shelf = 2–4 kb downstream (3′) of CpG island
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Clinical Epigenetics

ISSN: 1868-7083

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