Table 2 Lead variants for 27 significant association loci in the genome-wide association study meta-analysis of otosclerosis

From: Genome-wide screen of otosclerosis in population biobanks: 27 loci and shared associations with skeletal structure

Rsid

Chr

Position

Effect allele

Non-effect allele

EAF

Nearest Gene

Consequence

Meta-analysis OR (95% CI)

P-value

FinnGen OR (95% CI)

UKBB OR (95% CI)

EstBB OR (95% CI)

Q p-value

I2

rs77249084

8

116560300

G

A

0.3

EIF3H

Regulatory region

1.31 (1.24–1.38)

1.78E–23

1.44 (1.33–1.56)

1.21 (1.09–1.34)

1.22 (1.1–1.34)

0.0074

0.8

rs11868207

17

68679579

C

T

0.23

FAM20A (LINC01482)

Intergenic (Intronic)

1.34 (1.26–1.42)

1.25E–22

1.46 (1.33–1.6)

1.29 (1.16–1.43)

1.24 (1.11–1.38)

0.056

0.65

rs12270054

11

65555077

T

C

0.22

LTBP3

Intronic

0.75 (0.71–0.8)

4.29E–20

0.68 (0.61–0.74)

0.76 (0.69–0.85)

0.86 (0.77–0.97)

0.0074

0.8

rs10592836

14

103471816

C

CAAT

0.34

MARK3

Intronic

1.25 (1.19−1.32)

2.79E–18

1.35 (1.25–1.46)

1.2 (1.09–1.32)

1.16 (1.06–1.28)

0.032

0.71

rs71900142

10

30775253

G

GCTTCTGGCTTAAGC

0.41

ZNF438

Intergenic

0.82 (0.78–0.86)

1.20E–15

0.75 (0.7–0.81)

0.88 (0.81–0.97)

0.86 (0.78–0.94)

0.015

0.76

rs7995158

13

110459370

G

A

0.55

COL4A2 (COL4A2-AS2)

3’ UTR (Intronic)

0.82 (0.79–0.86)

1.81E–15

0.83 (0.78–0.89)

0.79 (0.72–0.86)

0.85 (0.78–0.93)

0.47

0

rs39375

7

103837624

C

A

0.41

RELN

Intronic

1.21 (1.15–1.27)

3.21E–14

1.27 (1.18–1.37)

1.14 (1.04–1.25)

1.18 (1.08–1.29)

0.15

0.47

rs791903

6

33734868

C

G

0.5

IP6K3

Intronic

0.83 (0.8–0.88)

1.15E–13

0.84 (0.79–0.91)

0.82 (0.75–0.89)

0.84 (0.76–0.92)

0.85

0

rs753138805

4

87845066

G

GGAAA

0.0033

MEPE

Frameshift

 

9.80E–14

21.5 (9.6–48.4)

NA

NA

NA

NA

rs181831514

4

87901594

T

C

0.0024

MEPE

Intergenic

12.3 (6.09–24.9)

2.87E–12

19.66 (8.92–43.33)

NA

2.04 (0.43–9.62)

0.011

0.85

rs4917

3

186619924

C

T

0.64

AHSG

Missense

0.84 (0.8–0.88)

3.35E–12

0.86 (0.8–0.92)

0.77 (0.7–0.85)

0.88 (0.8–0.97)

0.12

0.52

rs13192457

6

44887654

A

C

0.44

SUPT3H

Intronic

1.21 (1.14–1.28)

4.80E–11

1.3 (1.21–1.39)

1.07 (0.98–1.18)

NA

0.0013

0.9

rs4636903

16

54995451

T

C

0.12

IRX5

Intergenic

1.28 (1.19–1.39)

7.32E–11

1.35 (1.2–1.52)

1.36 (1.18–1.56)

1.14 (0.99–1.31)

0.12

0.52

rs67284550

16

1480948

T

C

0.42

PTX4

Downstream gene

1.17 (1.12–1.23)

1.43E–10

1.25 (1.16–1.34)

1.13 (1.03–1.24)

1.09 (1–1.2)

0.055

0.66

rs11683921

2

111714056

G

T

0.38

ANAPC1

Intronic

1.17 (1.11–1.23)

3.23E–10

1.21 (1.12–1.3)

1.13 (1.03–1.24)

1.15 (1.05–1.27)

0.49

0

rs553652

11

96200151

A

G

0.92

MAML2

Intronic

1.3 (1.2–1.42)

9.24E–10

1.35 (1.2–1.52)

1.31 (1.08–1.6)

1.21 (1.04–1.42)

0.55

0

rs73172296

13

42525753

A

G

0.11

TNFSF11

Intergenic

1.26 (1.17–1.36)

1.18E–09

1.25 (1.13–1.4)

1.42 (1.2–1.68)

1.19 (1.03–1.36)

0.27

0.23

rs485107

8

8723898

G

C

0.53

CLDN23

Intergenic

1.16 (1.1–1.21)

2.20E–09

1.17 (1.09–1.26)

1.15 (1.05–1.26)

1.14 (1.04–1.25)

0.92

0

rs2762049

13

50248227

C

G

0.39

KCNRG (DLEU1)

Intergenic (Intronic)

1.16 (1.1–1.22)

2.34E–09

1.19 (1.11–1.28)

1.12 (1.02–1.23)

1.15 (1.05–1.26)

0.58

0

rs4877080

9

89398813

A

T

0.28

SEMA4D

Intronic

0.83 (0.78–0.88)

3.60E–09

0.84 (0.78–0.91)

0.81 (0.73–0.89)

NA

0.52

0

rs201694067

1

219593023

T

TGA

0.33

ZC3H11B

Intergenic

1.19 (1.12–1.26)

4.30E–09

1.18 (1.09–1.27)

NA

1.22 (1.11–1.34)

0.54

0

rs6066825

20

48723580

G

A

0.32

PREX1

Intronic

1.16 (1.1–1.22)

1.20E–08

1.17 (1.08–1.27)

1.25 (1.14–1.37)

1.06 (0.96–1.17)

0.066

0.63

rs66487118

19

10142669

A

G

0.3

DNMT1

Intronic

1.16 (1.1–1.23)

1.76E–08

1.14 (1.05–1.24)

1.26 (1.15–1.39)

1.1 (0.99–1.21)

0.12

0.53

rs8105161

19

41333726

C

T

0.16

TGFB1

Intronic

0.83 (0.78–0.89)

2.71E–08

0.81 (0.74–0.89)

0.85 (0.75–0.97)

0.86 (0.76–0.96)

0.71

0

rs2118612

15

67108152

T

C

0.79

SMAD3

Intronic

0.85 (0.8–0.9)

3.34E–08

0.84 (0.77–0.92)

0.81 (0.73–0.91)

0.89 (0.79–0.99)

0.59

0

rs4464751

6

73707844

T

G

0.54

CD109

Intronic

1.14 (1.09–1.2)

3.58E–08

1.15 (1.07–1.24)

1.18 (1.07–1.29)

1.1 (1.01–1.2)

0.58

0

rs80339979

9

99889430

G

GA

0.64

STX17 (STX17-AS1)

Intergenic (Intronic)

1.15 (1.09–1.21)

3.66E–08

1.1 (1.03–1.19)

1.16 (1.05–1.27)

1.22 (1.11–1.34)

0.26

0.27

rs6066131

20

46941020

C

T

0.45

EYA2

Intronic

1.14 (1.09–1.2)

4.91E–08

1.17 (1.09–1.26)

1.13 (1.03–1.24)

1.11 (1.01–1.21)

0.57

0

  1. A total of 3,504 cases and 861,198 controls from FinnGen, Estonian Biobank and UK Biobank were included in the meta-analysis. A Bonferroni-corrected two-sided genome-wide p-value threshold of 5×10−8 was used to establish significance, accounting for multiple comparisons. For all loci, the nearest protein-coding gene is shown. RNA and antisense genes overlapping the lead variant are additionally shown in parentheses. In addition to the 27 lead variants from the meta-analysis, data (in italic) are presented for the frameshift variant rs753138805 in MEPE which was observed only in FinnGen and was not included in the meta-analysis. The p-value for Cochran’s Q test and the I2 statistic are reported for each lead variant. Chr chromosome, EA effect allele, EAF effect allele frequency, NEA non-effect allele, OR odds ratio, CI confidence interval.
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