Table 2 Novel genome-wide significant loci in European-only analysis

From: European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation

 

European Discovery

Multi-ancestry discovery

23andMe European replication (N = 2,904,664)

 

Variant

Chr:position

Alleles (EAF)

OR (CI)

P

N (studies)

P

N (studies)

OR (CI)

P

Gene

Pathway

rs301804b

1:8476441

G/C (0.30)

1.05 (1.03–1.07)

2.3E−09

698266 (39)

8.5E−09

707642 (43)

1.03 (1.02–1.03)

5.5E−16

RERE

Apoptosis

rs61776548

1:12091024

A/G (0.47)

1.04 (1.02–1.05)

4.2E−08

787144 (39)

1.4E−07

1008560 (44)

1.02 (1.01–1.02)

5.6E−09

TNFRSF1B

Cytokine signalling in immune response

rs12565349

1:110371629

G/C (0.15)

1.05 (1.03–1.07)

1.3E−08

862259 (39)

1.9E−07

1083670 (44)

1.03 (1.02–1.04)

5.8E−15

CSF1

Cytokine signalling in immune response

rs187080438

1:150374354

T/C (0.03)

1.17 (1.11–1.23)

3.7E−10

758729 (20)

2.2E−12

765209 (22)

1.14 (1.12–1.16)

2.0E−41

CTSS

Antigen presentation in immune response

rs146527530b

1:151059196

G/T (0.02)

1.27 (1.20–1.35)

5.5E−15

744128 (13)

7.4E−19

744128 (13)

1.25 (1.22–1.28)

1.5E−88

CTSS

Antigen presentation in immune response

rs115161931b

1:151063299

T/C (0.04)

1.18 (1.13–1.23)

1.0E−13

472565 (26)

3.2E−12

479045 (28)

1.09 (1.08–1.11)

2.0E−32

CTSS

Antigen presentation in immune response

rs71625130b

1:151625094

A/G (0.04)

1.23 (1.18–1.28)

2.4E−27

770827 (25)

7.2E−30

772963 (26)

1.17 (1.16–1.19)

1.7E−89

RORCc

Cytokine signalling in immune response

rs149199808b

1:151626396

T/C (0.03)

1.32 (1.26-1.38)

4.4E−30

756174 (19)

8.7E−34

762654 (21)

1.24 (1.22–1.26)

3.1E−134

RORC

Cytokine signalling in immune response

rs821429b

1:153275443

A/G (0.96)

0.86 (0.84–0.89)

5.9E−18

852224 (30)

8.2E−16

858704 (32)

0.91 (0.89–0.92)

2.7E−38

S100A7

Differentiation regulation incl. in the innate immune system

rs12138773

1:153843489

A/C (0.03)

1.11 (1.07–1.16)

2.3E−08

851937 (28)

1.3E−09

858417 (30)

1.07 (1.05–1.09)

3.5E−16

S100A12c

Regulation of inflammatory processes and immune response

rs67766926a,b

2:61163581

G/C (0.23)

1.05 (1.03–1.06)

5.7E−10

863063 (39)

2.9E−11

1084480 (44)

1.05 (1.04–1.05)

1.2E−41

AHSA2P

Protein folding

rs112385344

2:112275538

T/C (0.12)

1.06 (1.04–1.08)

2.8E−09

852837 (34)

3.9E−08

862213 (38)

1.04 (1.03–1.05)

1.5E−18

MERTKc

Inhibits TLR-mediated innate immune response

rs62193132

2:242788256

T/C (0.46)

1.04 (1.03–1.06)

1.5E−09

832761 (26)

7.1E−08

1052040 (30)

1.03 (1.02–1.03)

1.5E−19

NEU4

Sphingolipid metabolism

rs10833b

4:142654547

C/T (0.65)

1.04 (1.03–1.06)

7.3E−09

859747 (38)

6.0E−08

1081160 (43)

1.02 (1.02–1.03)

3.4E−15

IL15

Cytokine signalling in immune response

rs148161264b

5:14604521

G/C (0.04)

1.10 (1.07–1.14)

7.4E−10

850619 (29)

2.0E−08

857099 (31)

1.05 (1.03–1.06)

1.6E−08

OTULINL

Endoplasmic reticulum component

rs7701967

5:130059750

A/G (0.31)

0.95 (0.94–0.97)

3.4E−09

520344 (36)

3.6E−09

529720 (40)

0.99 (0.98–0.99)

1.1E−06

LYRM7

Mitochondrial respiratory chain complex assembly

rs4532376b

5:176774403

A/G (0.30)

1.04 (1.03–1.06)

3.5E−09

859747 (38)

2.3E−09

1081160 (43)

1.03 (1.02–1.03)

1.4E−18

RGS14

G-alpha signalling

rs72925996b

6:90930513

C/T (0.33)

0.96 (0.94–0.97)

3.2E−10

862259 (39)

5.4E−09

1083670 (44)

0.96 (0.95–0.96)

2.2E−44

BACH2

NF-kappaB proinflammatory signalling

rs989437

7:28830498

G/A (0.61)

0.96 (0.95–0.97)

6.1E−11

864982 (40)

1.0E−09

1086390 (45)

0.97 (0.96–0.97)

6.9E−31

CREB5c

AMPK & ATK signalling

rs34215892

8:21767240

A/G (0.03)

0.87 (0.83–0.90)

4.7E−11

436369 (24)

2.0E−09

442849 (26)

0.89 (0.88–0.91)

1.0E−36

DOK2

Immune response IL-23 signalling

rs118162691

8:21767809

A/C (0.05)

0.92 (0.89–0.94)

7.8E−09

856229 (30)

1.8E−07

862709 (32)

0.90 (0.88–0.91)

1.1E−44

DOK2

Immune response IL-23 signalling

rs7843258

8:141601542

C/T (0.82)

1.05 (1.04–1.07)

1.5E−09

859747 (38)

3.6E−10

1081160 (43)

1.04 (1.03–1.05)

7.0E−25

AGO2

siRNA-mediated gene silencing

rs7857407

9:33430707

A/T (0.40)

1.04 (1.02–1.05)

2.5E−08

864982 (40)

9.0E−09

1086390 (45)

1.03 (1.02–1.03)

5.1E−18

AQP3

Aquaporin-mediated transport

rs10988863

9:102331281

C/A (0.21)

0.95 (0.93–0.96)

5.1E−11

862259 (39)

3.0E−09

1083670 (44)

0.97 (0.97–0.98)

1.3E−13

NR4A3

Transcriptional activator

rs17368814

11:102748695

G/A (0.13)

0.95 (0.93–0.97)

1.4E−08

858117 (37)

6.8E−07

1078260 (41)

0.95 (0.95–0.96)

1.2E−27

MMP12

Extracellular matrix organisation

rs11216206

11:116843425

G/C (0.07)

1.10 (1.07–1.14)

5.5E−10

557183 (35)

2.9E−10

778595 (40)

1.04 (1.03–1.05)

8.5E−15

SIK3

LKB1 signalling

rs5005507b

12:94611908

C/G (0.74)

1.05 (1.03–1.06)

3.6E−09

859747 (38)

9.6E−08

1081160 (43)

1.03 (1.02–1.04)

2.7E−18

PLXNC1

Semaphorin interactions incl. in immune response

rs7147439

14:105523663

A/G (0.73)

0.96 (0.95–0.97)

4.7E−08

781909 (37)

6.6E−07

1003320 (42)

0.97 (0.96–0.97)

4.8E−24

GPR132

GPCR signalling

rs2542147

18:12775851

T/G (0.84)

0.95 (0.93–0.96)

1.5E−09

862470 (39)

7.5E−08

1083880 (44)

0.96 (0.95–0.97)

2.6E−26

PTPN2

Cytokine signalling in immune response

  1. The lead SNP at each independent locus is displayed, along with the results from the European-only discovery, multi-ancestry discovery and European replication. The top-ranked gene from our gene prioritisation is listed, along with a description of the pathway/function of the gene. The evidence implicating each gene is presented in Supplementary Data 11.
  2. Alleles are listed as Effect allele/other allele, the effect allele frequency (EAF) in Europeans (average EAF, weighted by the sample size of each cohort).
  3. Genome build = GRCh37/hg19.
  4. ars4643526 at the same locus was previously identified in the discovery analysis of Paternoster et al. 2. However, this association did not replicate in that study.
  5. bWhilst not identified in any GWAS AD papers, these loci have previously shown evidence for association with AD in supplementary material of methodological papers92,93.
  6. cOne of two or three tied genes at these loci are shown.
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