Table 1 Recessive associations

From: Mono- and biallelic variant effects on disease at biobank scale

Gene

Lead variant (GRCh38)

OMiM

n hom.

Type

ClinVar

Phenotype

P value R4

β R4

P value R6

β R6

P value without hom.

β without hom.

CLRN1

3:150928107:A:C

Reces.

6

pLoF

P/LP

Hereditary retinal dystrophy

5.90 × 10−16ˆ

701.1

2.40 × 10−18

648.3

0.57

0.48

Sensorineural hearing loss

2.50 × 10−08

13

2.44 × 10−09

15.2

  

CEP250

20:35504248:G:A

Reces.

5

Mis

 

Varicose veins

1.30 × 10−08

4.3

2.23 × 10−05

6.0

0.35

−0.10

TRIM37

17:59079879:T:C

Reces.

5

pLoF

 

Congenital malformation syndrome

3.00 × 10−10

37

1.80 × 10−20

110.0

0.70

−0.30

CERKL

2:181603943:G:C

NA

10

Mis

P/LP

Hereditary retinal dystrophy

1.30 ×  10−16

210

1.32 × 10−32

470.7

0.0035

2.70

         

(0.13)*

(0.9)*

CNGB1

16:57901371:T:A

Reces.

14

Mis

Confl.

Hereditary retinal dystrophy

2.00 × 10−10

120

1.02 × 10−22

359.7

0.11

1.19

EYS

6:63721375:TTCTGCATG:T

Reces.

12

pLoF

P/LP

Hereditary retinal dystrophy

3.80 × 10−19

220

1.07 × 10−26

471.0

0.19

0.90

C10orf90

10:126459169:G:A

NA

13

Mis

B

Sensorineural hearing loss

2.20 × 10−12

6

8.83 × 10−14

8.3

0.062

0.14

NPHS1

19:35851608:CAG:C

Reces.

13

pLoF

P

Nephrotic syndrome

6.20 × 10−22

34

9.85 × 10−41

72.4

0.0046

1.2

         

(0.0004)*

(1.3)*

    

Glomerulonephritis

1.30 × 10−19

32

    

SOD1

21:31667290:A:C

Both

9

Mis

Confl.

Motor neuron disease

1.30 × 10−08

120

1.76 × 10−19

214.0

0.17

0.82

PCK1

20:57563691:G:A

Reces.

25

Mis

Confl.

Glucose regulation and pancreatic secretion

4.60 × 10−08

9.8

1.80 × 10−12

28.4

0.22

−0.27

GJB2

13:20189546:AC:A

Both

26

pLoF

P

Sensorineural hearing loss

2.90 × 10−28

6.5

3.69 × 10−42

14.7

0.28

0.07

         

(0.03)*

(0.12)*

CASP7

10:113725526:T:C

NA

45

Mis

 

Other cataract

2.50 × 10−16

4.8

3.95 × 10−26

10.6

0.0035

0.25

 

Senile cataract

2.30 × 10−12

2.1

    
 

Medication related adverse effects (asthma or COPD)

9.80 × 10−11

1.5

    

CLCN1

7:143351678:C:T

Both

53

pLoF

Confl.

Diseases of myoneural junction and muscle

3.70 × 10−14

13

1.05 × 10−15

20.0

0.20

0.21

SERPINA1

14:94378610:C:T

Reces.

77

 

P

Emphysema

2.20 × 10−21

28

2.52 × 10−31

51.8

0.037

0.5

EBAG9

8:109551075:C:G

NA

339

Intronic

 

Female infertility

1.60 × 10−11

2

9.00 × 10−16

1.98

0.08

0.09

TMEM214

2:27037601:G:A

NA

14,561

Mis

 

Pain (limb, back, neck, head or abdomen)

3.80 × 10−11

−0.061

6.05 × 10−09

−0.1

0.22

0

FUT2

19:48703417:G:A

Reces.

2,5905

pLoF

B

Intestinal infectious diseases

4.00 × 10−09

−0.069

4.34 × 10−15

−0.2

0.06

0

IGHG3

14:105769806:G:A

NA

29,078

Mis

 

Immunodeficiency with predominantly antibody defects

4.40 × 10−08

0.5

3.23 × 10−05

0.6

0.45

−0.1

UGT1A6

2:233693556:A:C

NA

37,679

Mis

B

Cholelithiasis

1.50 × 10−11

0.077

7.01 × 10−23

0.2

0.31

0

INS

11:2159830:T:G

Both

115,123

Mis

B

Type 1 diabetes

1.20 × 10−41

0.24

9.95 × 10−80

0.6

0.07

0.2

  1. Reces., known recessive in OMIM; mis, missense; pLoF, probable loss-of-function; hom., homozygous individuals in FinnGen; P, pathogenic; LP, likely pathogenic; B, benign; Confl., conflicting evidence; COPD, chronic obstructive pulmonary disease; R4, FinnGen data release 4 (n =176,899); R6, FinnGen data release 6 (n = 234,553). Only the most significant variant is shown per locus. Lead variants are given as rsids and GRCh38 coordinates (chromosome, position in bp, reference and alternate allele, separated by ‘:’). The P values and β values in brackets with an asterisk refer to the repetition of the heterozygous test in R6 data after exclusion of compound heterozygous individuals. The P value of the CLRN1 variant’s association with retinal dystrophy in R4 data (marked with ^) is calculated with Fisher’s exact test as it did not converge in SAIGE with all homozygous individuals affected. EBAG9 is the only noncoding variant presented here, as we estimate that it is a variant that is more likely to be causal than the originally identified pLoF variant in PKHD1L1 (Supplementary Note 3). Variants in the bottom five rows (TMEM214 and below) overlap with known GWAS loci that are listed in Supplementary Table 5.
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