Table 1 a) Sequence variants associated with IDD (Ncase = 58,854, Nctrl = 922,958). b) Sequence variants associated with Dorsalgia (Ncase = 119,110, Nctrl = 909,847).

From: Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology

a) IDD Loci

Position (hg38)

rs name

EAa

OAa

Close gene

Annotation

Frqb

OR (95% CI)c

Pc

Pbonfd

1p21.1

chr1:102875460

rs4907985

A

T

COL11A1

Downstream

49.8

1.04 (1.03, 1.06)

3.9E−10

0.0044

1q23.5

chr1:183974675

rs3010044

C

A

COLGALT2

Intron

23.8

1.05 (1.04, 1.07)

2.0E−11

0.00045

1q32.1

chr1:198841735

rs71663412

T

TGA

MIR181A1HG

Indel

20.3

0.95 (0.93, 0.97)

4.7E−10

0.011

2p13.3

chr2:69345897

rs6722492*

T

C

GFPT1

Splice region

41.5

1.05 (1.04, 1.07)

2.2E−17

2.2E−11

″

chr2:70489467

rs2902345*

T

C

TGFA

Intron

45.5

1.05 (1.04, 1.07)

1.1E−17

2.6E−10

4p16.3

chr4:1171342

rs11247975*

G

T

SPON2

Missense

32.5

0.96 (0.94, 0.97)

6.5E−11

6.6E−05

″

chr4:1794909

rs3135842*

C

G

FGFR3

Intron

27.1

0.95 (0.93, 0.96)

4.0E−14

4.5E−07

6p21.31

chr6:34578783

rs2814982

T

C

C6orf106

Intergenic

11.9

1.09 (1.07, 1.11)

2.4E−17

1.6E−09

6p21.1

chr6:44478351

rs6929734

G

T

CDC5L

Intergenic

44.5

0.96 (0.94, 0.97)

2.6E−11

0.00059

7p21.1

chr7:19554541

rs2192477

G

A

TWISTNB

Intergenic

34.4

1.05 (1.04, 1.07)

5.3E−14

1.2E−06

7p12.3

chr7:45988978

rs1723939

T

C

IGFBP3

Intergenic

48.2

1.06 (1.05, 1.07)

1.6E−18

3.6E−11

7q31.32

chr7:123199913

rs28364172

A

G

SLC13A1

Stop gained

0.23

1.41 (1.25, 1.60)

2.5E−08

0.0053

8q13.2

chr8:68665402

rs16934882

A

C

C8orf34

Intron

19.9

1.06 (1.04, 1.07)

5.7E−12

0.00013

8q24.21

chr8:129707875

rs10110842*e

C

T

GSDMC

Regulatory region

27.4

1.07 (1.05, 1.09)

5.4E−08

>0.05

″

chr8:129726726

rs7826493*

G

A

GSDMC

Regulatory region

20.0

0.91 (0.89, 0.92)

2.8E−16

2.6E−22

9q22.32

chr9:93911476

rs58723578

T

C

BARX1

Intergenic

10.0

1.08 (1.06, 1.10)

1.4E−11

0.00033

10p12.1

chr10:27612430

rs2637326

G

T

MKX

Intergenic

51.1

0.95 (0.94, 0.96)

1.1E−15

2.6E−08

10q22.1

chr10:72012903

rs1871452

T

A

CHST3

3′UTR

39.1

0.92 (0.90, 0.93)

1.6E−39

1.8E−32

10q24.32

chr10:102868477

rs7098825

C

T

AS3MT

Upstream

10.2

0.94 (0.92, 0.96)

4.1E−09

0.047

11p15.3

chr11:13275014

rs11022742

C

T

ARNTL

Upstream

27.3

0.95 (0.94, 0.96)

4.3E−12

4.8E−05

11p15.2

chr11:15693077

rs4757353

C

T

LOC102724957

Intron

22.4

1.06 (1.04, 1.07)

2.4E−12

5.4E−05

12p12.1

chr12:23822285

rs12310519

T

C

SOX5

Intron

15.7

1.11 (1.10, 1.13)

4.8E−35

3.2E−27

14q13.3

chr14:36988829

rs28487989

C

T

SLC25A21

Intron

21.1

0.95 (0.93, 0.96)

3.2E−12

7.4E−05

14q32.13

chr14:94378610

rs28929474

T

C

SERPINA1

Missense

1.83

0.87 (0.83, 0.92)

1.1E−08

0.011

15q22.33

chr15:67078168

rs12901372*

G

C

SMAD3

Intron

47.0

0.94 (0.93, 0.95)

9.0E−17

2.0E−09

″

chr15:67083662

rs4776881*e

C

T

SMAD3

Intron

45.3

1.05 (1.03, 1.06)

7.2E−08

>0.05

17q23.3

chr17:63921519

rs2040347

A

G

GH1

Upstream

34.9

0.96 (0.94, 0.97)

9.8E−11

0.0011

19q13.32

chr19:45877067

rs35318830

G

T

FOXA3

Downstream

9.41

1.08 (1.05, 1.10)

7.3E−12

8.2E−05

20q11.22

chr20:35437976

rs143384

G

A

GDF5

5′UTR

45.7

1.04 (1.03, 1.06)

1.2E−10

0.0014

b) Dorsalgia Loci

Position (hg38)

rs name

EAa

OAa

Close gene

Annotation

Frqb

OR (95%CI)c

Pc

Pbonfd

1p21.1

chr1:102875460

rs4907985

A

T

COL11A1

Downstream

49.8

1.03 (1.02, 1.04)

2.6E−09

0.029

2q22.3

chr2:147879893

rs7560502

C

A

ACVR2A

Intron

17.6

0.96 (0.95, 0.97)

3.8E−10

0.0087

3p21.31

chr3:49651777

rs34762726

A

G

BSN

Missense

32.2

0.96 (0.95, 0.97)

1.1E−15

1.1E−09

3p13

chr3:71732370

rs73090626

C

T

EIF4E3

Upstream

9.24

1.05 (1.04, 1.07)

5.1E−10

0.0057

3q13.32

chr3:118057173

rs1995245

C

T

IGSF11

Intergenic

18.0

0.96 (0.95, 0.97)

2.5E−10

0.0056

4p16.3

chr4:1688915

rs4865462

G

A

FAM53A

Upstream

47.4

0.97 (0.96, 0.98)

7.8E−10

0.0089

6p21.31

chr6:34595387

rs205262

G

A

C6orf106

Intron

26.9

1.04 (1.03, 1.05)

2.4E−12

5.4E−05

7q34

chr7:140459051

rs2272095

G

C

MKRN1

Missense

27.4

0.97 (0.96, 0.98)

6.8E−10

0.0013

8q24.21

chr8:129707875

rs10110842*

C

T

GSDMC

Regulatory region

27.4

1.03 (1.02, 1.05)

2.2E−10

>0.05

″

chr8:129726726

rs7826493*

G

A

GSDMC

Regulatory region

20.0

0.96 (0.95, 0.97)

7.2E−14

3.1E−06

10q22.1

chr10:72001257

rs751450

A

G

CHST3

Intron

39.1

0.96 (0.95, 0.97)

1.0E−15

2.3E−08

18q12.2

chr18:37570563

rs9953231

A

G

CELF4

Upstream

22.8

1.03 (1.02, 1.05)

2.7E−09

0.031

18q23

chr18:79817501

rs71338065*

T

TCA

KCNG2

Intergenic

20.8

1.04 (1.03, 1.05)

2.2E−11

0.0005

″

chr18:79873271

rs76838079*e

T

C

KCNG2

Intron

16.5

0.97 (0.96, 0.98)

7.5E−08

>0.05

19q13.32

chr19:44908684

rs429358

C

T

APOE

Missense

17.0

0.96 (0.95, 0.97)

2.0E−11

2.0E−05

19q13.41

chr19:51270257

rs28536511

A

C

SIGLECL1

Downstream

30.1

0.97 (0.96, 0.98)

1.6E−10

0.0018

  1. Bold are loci with marker significant in both IDD (Table 1a) and dorsalgia (Table 1b).
  2. aEffect allele (EA) and other allele (OA).
  3. bAverage frequency of effect allele in the four cohorts.
  4. cOR and P value for an inverse-variance weighted meta-analysis of association results for the four cohorts.
  5. dP value after a variant class-specific Bonferroni adjustment18. *For this variant the P value and OR presented is adjusted for the effect of the other variant at the locus through conditional analysis.
  6. eSecond signal is not genome-wide significant. Results per cohort are in Supplementary Data 3, 4. Associations of these and correlated variants (r2≥ 0.8) with various traits listed in the GWAS catalog (https://www.ebi.ac.uk/gwas/) are in Supplementary Data 16 (IDD variants) and Supplementary Data 17 (dorsalgia variants).
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