Table 1 Loci reaching genome-wide significance with WMH burden in one or more genetic association model.

From: Cerebral small vessel disease genomics and its implications across the lifespan

         

Main effectsa

JMA (N = 48,524)

         

Model 1 (N = 50,970)

Model 2 (N = 48,524)

Region

Position

Nearest gene

Analysis

SNP

Local h2

Function

EA/OA

EAF

β

SE

P

β

SE

P

P

Novel

 17q21.31

43144218

NMT1§

EUR/TRANS

rs6503417

0.23%

Intronic

c/t

0.63

0.052

0.006

3.43E-19

0.054

0.006

4.85E-20

9.17E-20

 16q24.2

87227397

C16orf95

EUR/TRANS

rs12921170

0.17%

Intergenic

a/g

0.58

0.050

0.006

9.82E-18

0.049

0.006

4.91E-17

1.44E-16

 3q27.1

183363263

KLHL24

EUR/TRANS

rs6797002

0.12%

Intronic

c/t

0.73

0.049

0.007

8.18E-14

0.046

0.007

3.26E-12

3.12E-11

 5q14.2

82859065

VCAN

EUR/TRANS

rs17205972

0.07%

Intronic

t/g

0.20

0.049

0.007

4.76E-12

0.051

0.007

2.34E-12

4.19E-12

 2q32.1

188028317

CALCRL

EUR/TRANS

rs62172472

0.10%

Intergenic

g/a

0.79

0.047

0.007

3.67E-11

0.046

0.007

1.73E-10

2.24E-10

 5q23.2

121518378

LOC100505841

EUR/TRANS

rs2303655

0.03%

Downstream

t/c

0.78

0.048

0.007

4.03E-11

0.049

0.007

3.58E-11

1.28E-11

 16q12.1

51442679

SALL1

EUR/TRANS

rs1948948

0.02%

Intergenic

c/t

0.56

0.037

0.006

1.17E-10

0.037

0.006

2.06E-10

7.27E-10

 14q32.11

91884655

CCDC88C

EUR/TRANS

rs1285847

0.10%

Upstream

t/c

0.55

0.036

0.006

1.24E-10

0.039

0.006

1.30E-11

9.00E-11

 8p23.1

8179639

SGK223

EUR/TRANS

rs73184312

0.07%

Intronic

g/a

0.72

0.038

0.006

2.18E-09

0.035

0.006

4.51E-08

8.12E-08

 10q24.33

105507145

SH3PXD2A-AS1

EUR/TRANS

rs71471298

0.21%

Intronic

t/c

0.11

0.053

0.009

2.72E-09

0.051

0.009

2.91E-08

4.58E-08

 1q41

215137222

KCNK2b

TRANS

rs6540873

0.03%

Intergenic

a/c

0.61

0.027

0.007

1.37E-08

0.027

0.007

2.81E-08

4.31E-05

 10p14

11804452

ECHDC3c

AFR/TRANS

rs11257311

0.01%

Intronic

g/t

0.70

0.046

0.010

2.01E-08

0.186

0.032

4.29E-09

1.85E-02

 22q12.1

27887471

MN1

EUR

rs5762197

0.05%

Intergenic

c/a

0.71

0.039

0.007

2.67E-08

0.040

0.007

2.26E-08

1.01E-07

 15q22.31

65355468

RASL12

EUR

rs12443113

0.07%

Intronic

g/a

0.55

0.031

0.006

3.42E-08

0.029

0.006

3.43E-07

2.14E-06

 8p23.1

9628753

TNKS

EUR

rs11249945

0.11%

Intronic

a/g

0.35

0.034

0.006

3.60E-08

0.032

0.006

3.84E-07

9.58E-08

 14q22.1

52604843

NID2d

EUR

rs72680374

0.07%

Intergenic

t/a

0.63

0.032

0.006

5.45E-08

0.032

0.006

1.43E-07

2.42E-06

 8p23.1

11031472

XKR6

EUR

rs7004825

0.08%

Intronic

t/c

0.47

0.031

0.006

9.18E-08

0.032

0.006

4.59E-08

4.55E-08

 1p22.2

89286673

PKN2

EUR

rs786921

0.05%

Intronic

a/g

0.60

0.033

0.007

2.52E-07

0.037

0.007

2.97E-08

1.74E-05

Previously described

 17q25.1

73888354

TRIM65

EUR/TRANS

rs34974290

0.40%

Exonic

a/g

0.19

0.104

0.007

2.59E-46

0.104

0.007

1.27E-45

1.34E-45

 2p16.1

56128091

EFEMP1

EUR/TRANS

rs7596872

0.09%

Intronic

a/c

0.10

0.097

0.010

3.81E-24

0.097

0.010

2.45E-23

8.06E-22

 6q25.1

151018909

PLEKHG1

EUR/TRANS

rs6940540

0.07%

Intronic

g/t

0.41

0.045

0.006

7.17E-15

0.043

0.006

1.32E-13

1.70E-13

 2p21

43132224

HAAO

EUR/TRANS

rs73923006

0.05%

Intergenic

g/c

0.81

0.055

0.007

2.00E-14

0.053

0.007

4.28E-13

3.57E-12

 10q24.33

105459116

SH3PXD2A

EUR/TRANS

rs4630220

0.21%

Intronic

g/a

0.71

0.048

0.007

1.46E-13

0.048

0.007

2.00E-13

3.10E-13

 2q33.2

203780515

CARF1

EUR/TRANS

rs7603972

0.14%

Intronic

a/g

0.87

0.070

0.010

2.23E-13

0.069

0.010

1.55E-12

2.80E-11

 10q24.33

105610326

SH3PXD2A

EUR/TRANS

rs10786772

0.21%

Intronic

g/a

0.64

0.042

0.006

1.56E-12

0.042

0.006

2.26E-12

4.80E-11

 13q34

111043309

COL4A2

EUR/TRANS

rs55940034

0.04%

Intronic

g/a

0.29

0.037

0.006

4.49E-09

0.037

0.006

4.63E-09

2.68E-08

 14q32.2

100625902

DEGS2

EUR/TRANS

rs7157599

0.01%

Exonic

c/t

0.29

0.041

0.007

1.49E-08

0.042

0.007

6.76E-09

2.38E-06

  1. For each locus, the variant reaching the lowest P value in the fixed-effects transancestral meta-analysis or the fixed-effects Europeans-only meta-analysis, respectively, is shown.
  2. JMA joint meta-analysis, SNP single nucleotide polymorphism, EUR European, AFR African–American, TRANS transethnic, SNPs GW significant in both the analysis, association statistic from the TRANS analysis are shown, Local h2 local SNP heritability for the locus estimated from SNP-main-effects EUR only, EA effect allele, OA other allele, EAF effect allele frequency, β effect estimate, SE standard error, P P value.
  3. aMain effects are assessed in Model 1, adjusted for age, sex, principal components for population stratification, and total intracranial volume, and in Model 2, which is additionally adjusted for hypertension status.
  4. bLocus reaching GW significance in MR-MEGA meta-regression analysis; § the lead SNP is not in LD (r2 < 0.01) with the chr17q21 locus previously reported to be associated with WMH volume in stroke patients16.
  5. cLocus reaching GW significance in AFR-only and MR-MEGA meta-regression analysis.
  6. dAdditional locus reaching GW significance in the GCTA-COJO analysis for the main-effects model.
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