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Table 2 Association estimates for CpG sites at p < 1.0 × 10–5 identified in the meta-EWAS of T2D with four cohorts (n = 3428 total; N = 340 T2D cases)

From: DNA methylation of blood cells is associated with prevalent type 2 diabetes in a meta-analysis of four European cohorts

CpG site

Gene

ALSPAC (N = 1050)

LBC1936 (N = 915)

RSIII-1 (N = 728)

RS-Bios (N = 735)

Meta-analysis (N = 3428)

Beta

P

Beta

P

Beta

P

Beta

P

Beta

SE

P

Direction

I2

Phet

cg19693031b

TXNIP

− 0.022

5.93E−03

− 0.026

3.88E−06

− 0.019

1.86E−05

− 0.015

1.27E−03

− 0.019

2.59E−03

8.75E−14

− − − −

0.00

4.55E−01

cg06500161a,b

ABCG1

0.026

2.68E−04

0.024

5.18E−08

0.010

5.06E−03

0.008

9.90E−03

0.013

1.92E−03

2.34E−11

+ + + +

77.70

3.72E−03

cg16765088

SYNM

− 0.021

8.47E−03

− 0.014

4.20E−04

− 0.009

2.20E−02

− 0.009

5.43E−05

− 0.011

1.75E−03

5.50E−10

− − − −

0.00

4.29E−01

cg00574958a,b

CPT1A

− 0.005

3.60E−02

− 0.008

6.68E−05

− 0.018

6.19E−06

− 0.004

1.51E−01

− 0.007

1.25E−03

1.20E−08

− − − −

72.20

1.29E−02

cg24704287

MIR23A

− 0.009

1.41E−01

− 0.012

1.20E−02

− 0.012

6.71E−04

− 0.011

8.31E−04

− 0.011

1.97E−03

2.34E−08

− − − −

0.00

9.68E−01

cg00144180

HDAC4

0.012

5.61E−02

0.013

5.88E−04

0.019

3.67E−04

0.008

3.94E−02

0.012

2.23E−03

5.64E−08

+ + + +

4.70

3.69E−01

cg04567334

CDH23

− 0.001

7.81E−01

− 0.005

5.49E−02

− 0.007

1.89E−03

− 0.007

9.38E−05

− 0.006

1.18E−03

1.67E−07

− − − −

0.00

6.70E−01

cg10584271

ITIH1

− 0.007

3.58E−01

− 0.019

8.08E−04

− 0.017

2.92E−04

− 0.010

2.43E−02

− 0.014

2.63E−03

1.73E−07

− − − −

5.60

3.65E−01

cg26270261

KRT4

− 0.004

4.35E−01

− 0.011

8.41E−05

− 0.007

1.37E−02

− 0.004

8.07E−03

− 0.006

1.24E−03

5.68E−07

− − − −

31.10

2.25E−01

cg16575444

CX3CL1

0.001

7.90E−01

− 0.004

1.29E−01

− 0.006

7.51E−03

− 0.007

2.90E−05

− 0.006

1.22E−03

6.83E−07

+ − − −

0.00

4.54E−01

cg24512093

ROBO1

− 0.018

3.57E−02

− 0.009

7.87E−02

− 0.004

3.28E−01

− 0.011

1.06E−05

− 0.010

1.92E−03

7.16E−07

− − − −

16.50

3.09E−01

cg11983038a

Intergenic

− 0.027

8.44E−04

− 0.003

7.69E−01

− 0.007

2.44E−01

− 0.025

7.05E−06

− 0.017

3.38E−03

7.23E−07

− − − −

65.10

3.53E−02

cg25136644

ATG9B

− 0.010

8.33E−02

− 0.007

4.43E−02

− 0.005

2.25E−02

− 0.012

4.52E−05

− 0.007

1.44E−03

7.27E−07

− − − −

34.80

2.04E−01

cg20812370a

PBX1

− 0.017

2.53E−02

− 0.017

9.03E−05

− 0.003

1.51E−01

− 0.007

5.11E−04

− 0.007

1.34E−03

7.40E−07

− − − −

70.70

1.67E−02

cg24686009

RAP1B

− 0.002

3.16E−04

− 0.001

2.82E−02

− 0.003

3.34E−03

0.000

8.43E−01

− 0.002

3.83E−04

1.19E−06

− − − +

0.20

3.91E−01

cg11024682b

SREBF1

0.007

1.07E−01

0.007

1.95E−02

0.011

1.08E−03

0.006

1.48E−02

0.008

1.59E−03

1.33E−06

+ + + +

0.00

6.94E−01

cg06114363d

ZNF683

− 0.016

2.27E−02

− 0.012

5.08E−04

− 0.008

7.40E−03

?

?

− 0.010

2.16E−03

1.37E−06

− − − ?

0.00

5.30E−01

cg01963618

LOC285768

− 0.010

1.17E−01

− 0.011

5.08E−03

− 0.007

4.91E−02

− 0.007

1.77E−03

− 0.008

1.58E−03

1.55E−06

− − − −

0.00

8.01E−01

cg22680424

HCCA2

0.009

2.38E−01

0.013

6.20E−04

0.007

3.18E−02

0.006

8.16E−03

0.008

1.63E−03

2.16E−06

+ + + +

0.00

4.92E−01

cg19876302

Intergenic

− 0.020

2.27E−02

− 0.007

1.06E−01

− 0.010

2.21E−03

− 0.006

5.08E−03

− 0.008

1.70E−03

2.22E−06

− − − −

0.00

4.30E−01

cg08857797

VPS25

0.002

8.08E−01

0.012

1.09E−02

0.008

6.17E−03

0.008

2.53E−03

0.009

1.84E−03

2.28E−06

+ + + +

0.00

8.13E−01

cg27374726

Intergenic

− 0.006

2.35E−01

− 0.015

5.06E−04

− 0.004

2.66E−01

− 0.011

3.93E−04

− 0.009

1.83E−03

2.32E−06

− − − −

42.40

1.57E−01

cg09185884

KCTD2

0.011

2.94E−02

0.015

6.40E−02

0.013

4.18E−02

0.010

1.28E−03

0.011

2.31E−03

2.33E−06

+ + + +

0.00

9.19E−01

cg27115863

Intergenic

− 0.023

3.50E−03

− 0.006

2.40E−01

− 0.010

2.27E−02

− 0.012

1.23E−03

− 0.011

2.31E−03

2.41E−06

− − − −

13.40

3.25E−01

cg24795867

WNT5B

− 0.007

3.59E−01

− 0.002

6.13E−01

− 0.002

3.62E−01

− 0.008

5.51E−07

− 0.006

1.29E−03

2.47E−06

− − − −

43.20

1.52E−01

cg08945443

ZMYND17

− 0.006

3.92E−01

0.009

1.63E−01

0.015

6.67E−04

0.012

2.08E−04

0.010

2.23E−03

2.64E−06

− + + +

51.70

1.02E−01

cg06039489

C20orf26

0.008

3.03E−01

0.028

2.22E−03

0.010

1.39E−01

0.018

3.43E−04

0.016

3.35E−03

2.71E−06

+ + + +

16.80

3.08E−01

cg08570691

RPL13AP5

− 0.012

7.78E−02

− 0.010

3.93E−03

− 0.014

3.64E−04

− 0.004

8.95E−02

− 0.008

1.76E−03

2.78E−06

− − − −

42.60

1.56E−01

cg12593793

Intergenic

− 0.012

2.93E−02

− 0.011

1.17E−03

− 0.014

4.03E−04

− 0.003

2.27E−01

− 0.008

1.65E−03

2.90E−06

− − − −

60.50

5.54E−02

cg27037013

Intergenic

− 0.027

2.39E−02

− 0.025

7.68E−04

− 0.019

2.20E−03

− 0.007

1.41E−01

− 0.015

3.22E−03

2.90E−06

− − − −

51.90

1.01E−01

cg07212837

Intergenic

0.003

5.45E−01

0.008

6.22E−03

0.007

2.72E−02

0.006

1.93E−03

0.006

1.38E−03

3.28E−06

+ + + +

0.00

8.43E−01

cg16192197

Intergenic

0.007

4.31E−01

0.005

3.38E−01

0.009

1.75E−02

0.013

5.29E−05

0.010

2.06E−03

3.71E−06

+ + + +

0.00

5.03E−01

cg15560632

LRCH4

− 0.001

7.24E−03

− 0.001

3.40E−03

− 0.002

1.02E−02

− 0.001

1.62E−01

− 0.001

2.04E−04

3.83E−06

− − − −

3.50

3.75E−01

cg14003143a

SGK2

− 0.021

5.65E−04

− 0.007

1.49E−02

− 0.007

8.21E−03

− 0.004

3.85E−02

− 0.006

1.27E−03

4.12E−06

− − − −

62.60

4.54E−02

cg20154947

PLEC1

− 0.002

3.91E−04

− 0.002

1.49E−03

− 0.002

1.48E−01

0.000

7.36E−01

− 0.002

4.09E−04

4.34E−06

− − − −

23.40

2.71E−01

cg25741837

SMYD5

0.022

4.86E−03

0.007

9.85E−02

0.009

2.33E−02

0.009

4.74E−03

0.009

2.01E−03

4.76E−06

+ + + +

0.00

3.96E−01

cg26766064

MIR657

− 0.014

8.56E−02

− 0.010

7.14E−03

− 0.008

1.59E−02

− 0.005

6.10E−03

− 0.007

1.43E−03

5.17E−06

− − − −

0.00

4.12E−01

cg25536676

DHCR24

− 0.007

2.52E−01

− 0.012

1.48E−03

− 0.014

3.67E−04

− 0.004

8.16E−02

− 0.008

1.68E−03

5.39E−06

− − − −

54.80

8.42E−02

cg11376147b

SLC43A1

− 0.008

1.03E−02

− 0.004

5.34E−02

− 0.007

1.94E−02

− 0.005

1.45E−02

− 0.006

1.27E−03

5.43E−06

− − − −

0.00

7.64E−01

cg20316538

RUFY4

− 0.008

1.15E−01

− 0.007

7.53E−03

− 0.007

1.39E−02

− 0.004

1.06E−02

− 0.005

1.16E−03

6.11E−06

− − − −

0.00

6.05E−01

cg18181703c

SOCS3

− 0.024

7.42E−03

− 0.011

2.08E−02

− 0.016

2.85E−04

− 0.004

2.26E−01

− 0.010

2.31E−03

6.20E−06

− − − −

56.50

7.52E−02

cg11851382

PPAP2B

− 0.012

2.34E−02

− 0.012

3.79E−03

− 0.005

2.13E−01

− 0.006

5.87E−03

− 0.008

1.69E−03

6.42E−06

− − − −

0.00

4.91E−01

cg00162348

RNF40

− 0.002

1.79E−04

− 0.001

5.06E−02

− 0.003

4.86E−02

− 0.001

5.94E−01

− 0.002

4.23E−04

6.64E−06

− − − −

0.00

6.00E−01

cg07184465

SPZ1

− 0.012

3.83E−02

− 0.006

6.66E−02

− 0.011

1.40E−04

− 0.004

1.03E−01

− 0.007

1.55E−03

7.18E−06

− − − −

38.20

1.83E−01

cg14284506

Intergenic

− 0.009

8.08E−04

− 0.005

1.01E−03

− 0.003

2.51E−01

− 0.002

5.00E−01

− 0.005

1.08E−03

7.31E−06

− − − −

21.90

2.79E−01

cg11252555a

RPL13AP5

− 0.013

4.69E−02

− 0.010

3.55E−03

− 0.015

1.85E−04

− 0.003

2.03E−01

− 0.008

1.73E−03

7.44E−06

− − − −

63.30

4.25E−02

cg10082515

Intergenic

− 0.022

3.20E−03

− 0.006

5.79E−01

− 0.010

7.04E−02

− 0.014

1.56E−03

− 0.013

3.00E−03

7.46E−06

− − − −

0.00

5.05E−01

cg00896068

Intergenic

− 0.003

6.50E−01

− 0.011

7.96E−03

− 0.004

3.10E−01

− 0.009

1.79E−04

− 0.008

1.74E−03

7.58E−06

− − − −

0.00

4.82E−01

cg01577083

Intergenic

− 0.018

4.64E−03

− 0.012

4.99E−02

− 0.008

5.13E−02

− 0.012

1.44E−02

− 0.011

2.54E−03

7.93E−06

− − − −

0.00

6.21E−01

cg00320980

Intergenic

− 0.006

3.44E−01

− 0.007

8.21E−02

− 0.012

2.75E−03

− 0.010

4.24E−03

− 0.009

2.09E−03

7.97E−06

− − − −

0.00

7.44E−01

cg20231084

Intergenic

− 0.011

1.12E−01

− 0.008

1.78E−02

− 0.005

6.20E−02

− 0.006

2.49E−03

− 0.006

1.39E−03

8.36E−06

− − − −

0.00

7.96E−01

cg15832662

RTN3

− 0.010

1.70E−01

− 0.012

6.91E−03

− 0.012

5.16E−02

− 0.008

5.65E−03

− 0.009

2.08E−03

8.45E−06

− − − −

0.00

8.29E−01

cg13178597

RGS17

− 0.018

1.41E−02

− 0.005

4.64E−01

− 0.009

2.36E−02

− 0.011

1.60E−03

− 0.010

2.27E−03

8.57E−06

− − − −

0.00

5.80E−01

cg20116935

SEMA3B

− 0.015

3.85E−03

− 0.005

5.45E−02

− 0.006

6.60E−02

− 0.005

6.69E−03

− 0.006

1.38E−03

8.89E−06

− − − −

4.80

3.69E−01

cg00989505

MIR299

0.003

5.16E−01

− 0.004

1.00E−01

− 0.006

4.00E−04

− 0.004

6.73E−03

− 0.004

9.41E−04

9.33E−06

+ − − −

14.80

3.18E−01

cg07068382

MTCH1

0.000

9.91E−01

0.020

1.38E−04

0.011

1.32E−02

0.007

3.60E−02

0.010

2.37E−03

9.46E−06

− + + +

46.70

1.31E−01

cg14476101b

PHGDH

− 0.021

4.05E−02

0.000

9.46E−01

− 0.021

2.41E−04

− 0.017

4.72E−03

− 0.015

3.36E−03

9.46E−06

− − − −

52.00

1.00E−01

cg20456243

SPEG

− 0.015

6.49E−02

− 0.004

2.74E−01

− 0.010

3.31E−03

− 0.007

3.41E−03

− 0.007

1.65E−03

9.99E−06

− − − −

0.00

4.90E−01

  1. Associations described correspond to the main meta-EWAS model (model 1) adjusted for age, sex, SVs, cellular heterogeneity and smoking. Highlighted in bold are associations at p < 1.33 × 10–7. Direction of effect for each CpG is indicated for EWAS in ALSPAC, LBC1936, RSIII-1 and RS-Bios, respectively. I2 is the heterogeneity statistic. High heterogeneity if I2 > 40% and Phet < 0.05
  2. aCpGs identified with high heterogeneity in the meta-analysis
  3. bCpGs discovered in association with incident T2D, and later validated in studies of prevalent T2D by Cardona et al. [23]
  4. cCpG identified in association with incident T2D by Chambers et al. [22]
  5. dIn RS-Bios, estimates of the EWAS for the CpG cg06114363 (ZNF683) did not surpass QC prior to meta-analysis