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Table 2 Genome-wide significant associations for cognitive domain scores

From: A genome-wide search for pleiotropy in more than 100,000 harmonized longitudinal cognitive domain scores

Chr

Position

Variant

A1/A2a (MAF)

Nearest Gene

Cognitive Domain

Cohortsb

Genetic effects

βG (SE)

PG

βG×Age (SE)

PG×Age

PJoint

1

207573951

rs1752684

A/G (0.198)

CR1

Executive Function

All

-0.028 (0.007)

1.53 × 10–4

-0.002 (0.001)

6.05 × 10–3

5.05 × 10–5

Clinic

-0.042 (0.012)

5.91 × 10–4

-0.002 (0.001)

7.52 × 10–2

6.88 × 10–4

Community

-0.020 (0.009)

2.98 × 10–2

-0.002 (0.001)

4.90 × 10–2

2.40 × 10–2

Language

All

-0.026 (0.007)

3.90 × 10–4

-0.001 (0.001)

6.84 × 10–2

6.25 × 10–4

Clinic

-0.054 (0.012)

1.26 × 10–5

-0.002 (0.001)

5.07 × 10–2

1.63 × 10–5

Community

-0.011 (0.009)

2.14 × 10–1

-0.001 (0.001)

5.59 × 10–1

4.20 × 10–1

Memory

All

-0.043 (0.008)

1.75 × 10–7

-0.002 (0.001)

1.83 × 10–2

4.42 × 10–7

Clinic

-0.080 (0.014)

2.44 × 10–8

-0.004 (0.001)

1.05 × 10–2

8.85 × 10–9

Community

-0.022 (0.010)

2.46 × 10–2

0.000 (0.001)

6.45 × 10–1

6.88 × 10–2

2

127135234

rs6733839

T/C (0.403)

BIN1

CYP27C1

Executive Function

All

-0.009 (0.006)

1.25 × 10–1

0.000 (0.001)

6.54 × 10–1

2.92 × 10–1

Clinic

-0.023 (0.010)

1.77 × 10–2

0.000 (0.001)

6.84 × 10–1

5.58 × 10–2

Community

-0.001 (0.007)

8.70 × 10–1

0.000 (0.001)

9.27 × 10–1

9.84 × 10–1

Language

All

-0.031 (0.006)

6.90 × 10–8

-0.002 (0.001)

3.62 × 10–3

2.70 × 10–8

Clinic

-0.063 (0.010)

4.23 × 10–10

-0.001 (0.001)

2.09 × 10–1

1.98 × 10–9

Community

-0.017 (0.007)

1.68 × 10–2

-0.002 (0.001)

1.70 × 10–2

6.57 × 10–3

Memory

All

-0.039 (0.006)

2.20 × 10–9

-0.002 (0.001)

1.62 × 10–3

2.37 × 10–9

Clinic

-0.068 (0.012)

5.23 × 10–9

-0.001 (0.001)

2.08 × 10–1

1.60 × 10–8

Community

-0.027 (0.008)

5.71 × 10–4

-0.002 (0.001)

1.69 × 10–2

1.11 × 10–3

7

91069758

rs705353

G/A (0.252)

CDK14

Executive Function

All

0.003 (0.006)

6.40 × 10–1

-0.002 (0.001)

1.53 × 10–3

4.58 × 10–3

Clinic

0.000 (0.011)

9.75 × 10–1

-0.005 (0.001)

2.03 × 10–5

1.12 × 10–4

Community

0.006 (0.008)

4.20 × 10–1

-0.001 (0.001)

4.11 × 10–1

4.43 × 10–1

Language

All

0.007 (0.006)

2.68 × 10–1

-0.002 (0.001)

5.14 × 10–4

5.93 × 10–4

Clinic

-0.004 (0.011)

7.53 × 10–1

-0.007 (0.001)

2.54 × 10–9

1.73 × 10–8

Community

0.015 (0.008)

5.28 × 10–2

0.000 (0.001)

8.28 × 10–1

1.41 × 10–1

Memory

All

-0.003 (0.007)

6.95 × 10–1

-0.002 (0.001)

3.03 × 10–2

8.72 × 10–2

Clinic

-0.008 (0.013)

5.46 × 10–1

-0.005 (0.001)

1.36 × 10–4

6.11 × 10–4

Community

0.005 (0.009)

5.93 × 10–1

0.000 (0.001)

9.19 × 10–1

8.59 × 10–1

8

30963282

rs117523305

C/G (0.016)

PURG

TEX15

Executive Function

All

-0.001 (0.022)

9.67 × 10–1

-0.006 (0.002)

5.35 × 10–3

2.02 × 10–2

Clinic

-0.012 (0.038)

7.42 × 10–1

-0.002 (0.004)

5.89 × 10–1

8.23 × 10–1

Community

0.003 (0.026)

9.13 × 10–1

-0.008 (0.003)

2.65 × 10–3

9.18 × 10–3

Language

All

-0.018 (0.021)

4.02 × 10–1

-0.008 (0.002)

8.23 × 10–4

3.01 × 10–3

Clinic

0.028 (0.039)

4.80 × 10–1

-0.001 (0.004)

7.03 × 10–1

7.11 × 10–1

Community

-0.041 (0.025)

1.19 × 10–1

-0.011 (0.003)

9.16 × 10–5

1.87 × 10–4

Memory

All

-0.069 (0.024)

5.27 × 10–3

-0.010 (0.002)

5.18 × 10–5

3.62 × 10–5

Clinic

-0.041 (0.044)

3.60 × 10–1

0.004 (0.004)

3.34 × 10–1

3.88 × 10–1

Community

-0.098 (0.029)

7.87 × 10–4

-0.018 (0.003)

1.41 × 10–8

1.73 × 10–8

11

60173126

rs7232

A/T (0.361)

MS4A6A

Executive Function

All

0.012 (0.006)

3.46 × 10–2

0.002 (0.001)

2.90 × 10–3

2.38 × 10–3

Clinic

0.021 (0.010)

3.46 × 10–2

0.000 (0.001)

8.60 × 10–1

1.06 × 10–1

Community

0.009 (0.007)

2.07 × 10–1

0.002 (0.001)

6.28 × 10–4

2.09 × 10–3

Language

All

0.016 (0.006)

6.40 × 10–3

0.002 (0.001)

1.04 × 10–4

3.61 × 10–5

Clinic

0.045 (0.010)

1.40 × 10–5

0.002 (0.001)

4.91 × 10–2

1.55 × 10–5

Community

0.003 (0.007)

6.38 × 10–1

0.002 (0.001)

1.93 × 10–3

6.31 × 10–3

Memory

All

0.027 (0.006)

5.19 × 10–5

0.003 (0.001)

2.60 × 10–5

9.43 × 10–7

Clinic

0.068 (0.012)

1.25 × 10–8

0.001 (0.001)

2.27 × 10–1

3.97 × 10–8

Community

0.011 (0.008)

1.50 × 10–1

0.003 (0.001)

4.62 × 10–4

1.80 × 10–3

11

127595711

rs145012974

A/G (0.014)

LINC02712

LINC02098

Executive Function

All

-0.040 (0.024)

1.03 × 10–1

-0.007 (0.002)

4.72 × 10–3

7.25 × 10–3

Clinic

-0.013 (0.041)

7.53 × 10–1

-0.004 (0.004)

3.14 × 10–1

5.72 × 10–1

Community

-0.056 (0.030)

6.46 × 10–2

-0.008 (0.003)

5.11 × 10–3

6.48 × 10–3

Language

All

-0.029 (0.024)

2.29 × 10–1

-0.014 (0.002)

7.69 × 10–9

3.66 × 10–8

Clinic

-0.026 (0.041)

5.31 × 10–1

-0.012 (0.004)

2.16 × 10–3

7.23 × 10–3

Community

-0.033 (0.029)

2.70 × 10–1

-0.016 (0.003)

1.00 × 10–6

3.29 × 10–6

Memory

All

-0.052 (0.026)

5.08 × 10–2

-0.008 (0.003)

2.46 × 10–3

3.99 × 10–3

Clinic

-0.051 (0.047)

2.87 × 10–1

-0.010 (0.005)

3.06 × 10–2

5.42 × 10–2

Community

-0.050 (0.032)

1.24 × 10–1

-0.007 (0.003)

3.00 × 10–2

6.31 × 10–2

17

19806731

rs157405

G/A (0.023)

ULK2

Executive Function

All

0.063 (0.018)

8.61 × 10–4

0.008 (0.002)

1.04 × 10–5

1.49 × 10–6

Clinic

-0.024 (0.032)

4.62 × 10–1

0.002 (0.003)

4.25 × 10–1

5.20 × 10–1

Community

0.107 (0.023)

3.21 × 10–6

0.011 (0.002)

7.65 × 10–7

2.19 × 10–9

Language

All

0.029 (0.018)

1.19 × 10–1

0.002 (0.002)

2.04 × 10–1

1.70 × 10–1

Clinic

-0.040 (0.033)

2.29 × 10–1

0.002 (0.003)

4.81 × 10–1

3.35 × 10–1

Community

0.059 (0.022)

8.39 × 10–3

0.003 (0.002)

2.54 × 10–1

2.21 × 10–2

Memory

All

0.046 (0.020)

2.78 × 10–2

0.001 (0.002)

5.87 × 10–1

8.07 × 10–2

Clinic

-0.005 (0.038)

9.07 × 10–1

0.002 (0.004)

5.39 × 10–1

8.14 × 10–1

Community

0.064 (0.024)

9.43 × 10–3

0.001 (0.003)

6.48 × 10–1

2.71 × 10–2

17

44352876

rs5848

T/C (0.305)

GRN

Executive Function

All

-0.007 (0.006)

2.53 × 10–1

-0.002 (0.001)

1.32 × 10–4

5.43 × 10–4

Clinic

0.003 (0.010)

7.50 × 10–1

-0.003 (0.001)

4.56 × 10–3

1.67 × 10–2

Community

-0.012 (0.008)

1.14 × 10–1

-0.002 (0.001)

5.76 × 10–3

1.15 × 10–2

Language

All

-0.012 (0.006)

5.99 × 10–2

-0.002 (0.001)

2.86 × 10–3

3.53 × 10–3

Clinic

-0.015 (0.011)

1.71 × 10–1

-0.001 (0.001)

4.67 × 10–1

3.11 × 10–1

Community

-0.011 (0.007)

1.34 × 10–1

-0.003 (0.001)

1.56 × 10–3

3.43 × 10–3

Memory

All

-0.029 (0.007)

2.19 × 10–5

-0.003 (0.001)

1.07 × 10–6

4.21 × 10–8

Clinic

-0.032 (0.012)

9.58 × 10–3

-0.003 (0.001)

3.30 × 10–3

5.28 × 10–4

Community

-0.028 (0.008)

8.11 × 10–4

-0.003 (0.001)

1.29 × 10–4

6.50 × 10–5

19c

44908684

rs429358

C/T (0.231)

APOE

Executive Function

All

-0.192 (0.008)

6.75 × 10–135

-0.009 (0.001)

1.26 × 10–28

8.58 × 10–145

Clinic

-0.308 (0.011)

5.51 × 10–166

-0.010 (0.001)

1.71 × 10–19

1.86 × 10–170

Community

-0.089 (0.010)

5.21 × 10–17

-0.006 (0.001)

4.58 × 10–9

7.05 × 10–20

Language

All

-0.193 (0.008)

1.81 × 10–137

-0.011 (0.001)

5.99 × 10–45

2.99 × 10–158

Clinic

-0.334 (0.011)

7.15 × 10–187

-0.016 (0.001)

2.15 × 10–46

3.89 × 10–206

Community

-0.079 (0.010)

2.00 × 10–14

-0.006 (0.001)

5.59 × 10–7

2.52 × 10–16

Memory

All

-0.323 (0.008)

2.16 × 10–298

-0.017 (0.001)

2.19 × 10–76

7.51 × 10–321

Clinic

-0.536 (0.013)

2.38 × 10–359

-0.017 (0.001)

8.14 × 10–38

3.31 × 10–374

Community

-0.168 (0.011)

3.45 × 10–47

-0.012 (0.001)

1.00 × 10–22

4.04 × 10–51

19c

44908822

rs7412

T/C (0.059)

APOE

Executive Function

All

0.063 (0.011)

2.78 × 10–8

0.005 (0.001)

5.40 × 10–6

8.28 × 10–11

Clinic

0.180 (0.020)

2.98 × 10–18

0.002 (0.002)

2.73 × 10–1

1.42 × 10–17

Community

0.016 (0.013)

2.39 × 10–1

0.005 (0.001)

6.71 × 10–5

2.88 × 10–4

Language

All

0.055 (0.011)

9.77 × 10–7

0.004 (0.001)

1.40 × 10–4

2.93 × 10–8

Clinic

0.194 (0.021)

1.23 × 10–19

0.007 (0.002)

1.95 × 10–4

1.19 × 10–21

Community

0.001 (0.013)

9.51 × 10–1

0.002 (0.001)

2.35 × 10–1

4.67 × 10–1

Memory

All

0.105 (0.012)

9.64 × 10–17

0.008 (0.001)

1.11 × 10–9

1.11 × 10–19

Clinic

0.302 (0.025)

5.81 × 10–34

0.005 (0.002)

2.09 × 10–2

1.18 × 10–34

Community

0.040 (0.015)

6.93 × 10–3

0.006 (0.002)

9.90 × 10–5

1.73 × 10–4

  1. aA1 Minor allele, A2 Reference allele, MAF Minor allele frequency
  2. bAll Total sample, Clinic Clinic-based cohorts, Community Community-based cohorts
  3. cWe presented GWAS results for the APOE SNPs—ε4 (rs429358) and ε2 (rs7412) alleles—but excluded all the other results in the APOE region
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Molecular Neurodegeneration

ISSN: 1750-1326