Table 2 Association statistics of the 29 tested AD-associated variants

From: Centenarian controls increase variant effect sizes by an average twofold in an extreme case–extreme control analysis of Alzheimer’s disease

Chr

Position

Rs ID

Gene

A1

\({\mathrm{log}}\,{\mathrm{OR}}_{\mathrm{l}}^{\mathrm{k}}\)(SE)

\({\mathrm{log}}\,{\mathrm{OR}}_{{\mathrm{EA}} - {\mathrm{EC}}}^{\mathrm{k}}\)(SE)

P valueEA–EC

\({\mathrm{E}}_{{\mathrm{EA}} - {\mathrm{EC}}}^{\mathrm{k}}\) (95% CI, p)

AFEA

AFNC

AFEC

6

41,129,252

rs75932628

TREM2 (R47H)

T

0.89 (0.09)

5.75 (5.13)

2.63 × 10−1

6.46 (− 4.83–18.46, 3.5×10−1)

0.003

0.001

0.000

10

11,720,308

rs7920721

ECHDC3

G

0.07 (0.01)

0.31 (0.10)

2.93 × 10−3 *

4.56 (1.55–8.93, 1.8 × 10−2)

0.430

0.389

0.357

14

92,926,952

rs10498633

SLC24A4-RIN3

T

− 0.09 (0.01)

− 0.42 (0.11)

1.30 × 10−4 *

4.50 (2.08– 7.93, 2.8 × 10−3)

0.206

0.236

0.292

7

37,841,534

rs2718058

NME8

G

− 0.08 (0.01)

− 0.29 (0.10)

3.72 × 10−3 *

3.80 (1.17– 7.28, 3.3 × 10−2)

0.360

0.367

0.433

16

81,942,028

rs72824905

PLCG2

G

− 0.39 (0.06)

− 1.27 (0.40)

1.38 × 10−3 *

3.28 (1.26–5.98, 2.8×10−2)

0.008

0.012

0.025

6

32,578,530

rs9271192

HLA-DRB1

A

− 0.11 (0.01)

− 0.35 (0.16)

3.06 × 10−2 *

3.20 (0.35–6.65, 1.3 × 10−1)

0.712

0.727

0.780

7

100,004,446

rs1476679

ZCWPW1

T

0.09 (0.01)

0.26 (0.11)

1.34 × 10−2 *

2.97 (0.60−6.10, 1.0 × 10−1)

0.703

0.674

0.649

19

1,063,443

rs4147929

ABCA7 (A>G)

G

− 0.14 (0.02)

− 0.32 (0.14)

2.11 × 10−2 *

2.26 (0.30–4.42, 2.2 × 10−1)

0.809

0.834

0.855

19

45,412,079

rs7412

APOE (ε2)

T

− 0.79 (0.03)

− 1.76 (0.18)

3.16 × 10−21 *

2.24 (1.75–2.77, 1.4 × 10−7)

0.033

0.091

0.149

4

11,711,232

rs13113697

HS3ST1

G

− 0.07 (0.01)

− 0.14 (0.12)

2.41 × 10−1

2.06 (− 1.49–6.13, 5.4×10−1)

0.265

0.268

0.247

17

47,297,297

rs616338

ABI3

C

− 0.36 (0.05)

− 0.74 (0.57)

1.93 × 10−1

2.06 (− 0.99–5.59, 5.2 × 10−1)

0.017

0.009

0.006

6

47,487,762

rs10948363

CD2AP

G

0.10 (0.01)

0.19 (0.11)

8.84 × 10−2

2.00 (− 0.34–4.60, 4.1×10−1)

0.284

0.272

0.245

19

45,411,941

rs429358

APOE (ε4)

C

1.05 (0.03)

2.08 (0.17)

1.31 × 10−33 *

1.99 (1.65–2.33, 1.5 × 10−9)

0.429

0.166

0.082

7

143,110,762

rs11771145

EPHA1

A

− 0.10 (0.01)

− 0.20 (0.10)

5.96 × 10−2

1.94 (− 0.09–4.29, 3.7 × 10−1)

0.325

0.345

0.371

11

47,557,871

rs10838725

CELF1

C

0.08 (0.01)

0.14 (0.11)

2.05 × 10−1

1.78 (− 0.95–5.11, 5.8 × 10−1)

0.328

0.314

0.302

8

27,195,121

rs28834970

PTK2B

C

0.10 (0.01)

0.18 (0.10)

8.96 × 10−2

1.76 (− 0.23–4.09, 4.7×10−1)

0.395

0.376

0.353

11

59,923,508

rs983392

MS4A6A

G

− 0.11 (0.01)

− 0.17 (0.10)

9.39 × 10−2

1.56 (− 0.20–3.61, 5.4 × 10−1)

0.397

0.403

0.439

11

121,435,587

rs11218343

SORL1

C

− 0.26 (0.03)

− 0.39 (0.25)

1.21 × 10−1

1.48 (− 0.39–3.51, 6.2 × 10−1)

0.033

0.040

0.047

2

127,892,810

rs6733839

BIN1

T

0.20 (0.01)

0.25 (0.10)

1.12 × 10−2 *

1.28 (0.31–2.29, 5.8 × 10−1)

0.456

0.413

0.390

11

85,867,875

rs10792832

PICALM

G

0.14 (0.01)

0.15 (0.10)

1.26 × 10−1

1.09 (− 0.30–2.56, 9.1 × 10−1)

0.653

0.614

0.612

20

55,018,260

rs7274581

CASS4

C

− 0.13 (0.02)

− 0.14 (0.18)

4.41 × 10−1

1.06 (−1.83–4.07, 9.7 × 10−1)

0.075

0.088

0.084

6

41,129,207

rs143332484

TREM2 (R62H)

T

0.50 (0.07)

0.48 (0.48)

3.21 × 10−1

0.97 (− 0.96–3.09, 9.8 × 10−1)

0.017

0.015

0.009

17

44,353,222

rs118172952

KANSL1

G

− 0.14 (0.03)

− 0.13 (0.14)

3.44 × 10−1

0.97 (−1.08−3.64, 9.6 × 10−1)

0.191

0.202

0.221

1

207,692,049

rs6656401

CR1

G

− 0.17 (0.01)

− 0.12 (0.12)

3.11 × 10−1

0.75 (− 0.75–2.21, 7.4 × 10−1)

0.781

0.803

0.806

19

1,061,892

rs200538373

ABCA7 (G>C)

C

− 0.65 (0.14)

− 0.44 (0.80)

5.81 × 10−1

0.68 (− 1.83–3.54, 7.9 × 10−1)

0.004

0.004

0.006

8

27,467,686

rs9331896

CLU

T

0.15 (0.01)

0.09 (0.10)

3.99 × 10−1

0.60 (− 0.78–2.06, 5.8 × 10−1)

0.361

0.400

0.378

2

234,068,476

rs35349669

INPP5D

T

0.08 (0.01)

0.03 (0.10)

7.83 × 10−1

0.36 (− 2.33–3.16, 6.2 × 10−1)

0.474

0.496

0.486

14

53,400,629

rs17125944

FERMT2

C

0.13 (0.02)

− 0.11 (0.16)

4.99 × 10−1

− 0.82 (− 3.46–1.60, 1.3×10−1)

0.104

0.105

0.114

5

88,223,420

rs190982

MEF2C

A

0.08 (0.01)

− 0.14 (0.10)

1.70 × 10−1

− 1.86 (− 5.01–0.77, 3.3 × 10−2)

0.408

0.406

0.372

Average

       

1.90 ± 0.29, p = 9.0 x 10−4

   
  1. Chr, chromosome; Position, chromosomal position (GRCh37); Rs ID, variant ID; Gene, gene associated with the variant according to paper in which the variant was found; A1, tested allele (alternative allele according to Haplotype Reference Consortium (HRC) panel); \(\log OR_l^k\)(SE), log(odds ratio) and relative standard error for variant k reported by study with largest sample size; \(\log OR_{EA - EC}^k\) (SE), log(odds ratio) and relative standard error in extreme control association; P value, p value of AD association of extreme AD cases vs centenarian controls; \(E_{EA - EC}^k\) (95% CI, p), change in effect size, 95% confidence intervals and p value of difference when using extreme phenotypes relative to published effect sizes; AFEA , tested allele frequency in AD extreme cases; AFNC, tested allele frequency in normal controls; AFEC, tested allele frequency in centenarian controls. Bold: variants for which the EkEA-EC was significantly different from published effect size; *: significant at p < 0.05
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