Table 2 Statistically significant associations from the European ancestry analysis.

From: Genome-wide rare variant analysis for thousands of phenotypes in over 70,000 exomes from two cohorts

Method

Lead gene

Lead phenotype

Lead model

UKB carrier n (%)b

UKB p value

HNP carrier n (%)b

HNP p value

Meta p value

LMM

ALPL

Alkaline phosphatasea

Coding

257 (0.68%)

2.4 × 10−186

68 (0.65%)

2.5 × 10−39

5.3 × 10−223

LMM

SLC22A12

Uratea

Coding

314 (0.83%)

3.3 × 10−108

8 (0.46%)

2.1 × 10−4

5.5 × 10−111

LMM

GOT1

Aspartate aminotransferase

Coding

113 (0.3%)

5.4 × 10−58

28 (0.27%)

2.2 × 10−13

1.6 × 10−69

LMM

ABCA1

HDL cholesterola

Coding

449 (1.26%)

2.9 × 10−35

88 (0.98%)

2.3 × 10−10

4.9 × 10−44

LMM

APOB

LDL directa

LoF

96 (0.25%)

8.9 × 10−31

8 (0.09%)

9.7 × 10−11

8.5 × 10−40

LMM

GPT

Alanine aminotransferase

Coding

126 (0.33%)

1.9 × 10−28

40 (0.39%)

2.4 × 10−6

4.0 × 10−33

FET

HBB

Thalassaemia

LoF

1 (25%) /0 (0%)b

1.2 × 10−4

8 (47.06%)/5 (0.03%)b

1.7 × 10−21

1.2 × 10−24

LMM

TUBB1

Platelet counta

Coding

233 (0.59%)

1.2 × 10−15

71 (0.66%)

2.9 × 10−7

2.8 × 10−21

FET

JAK2

D45 Polycythaemia vera

Coding

13 (36.11%)/209 (0.61%)b

1.7 × 10−19

3 (10.34%)/77 (0.53%)b

5.4 × 10−4

1.7 × 10−19

LMM

KLF1

Mean corpuscular haemoglobin

LoF

27 (0.07%)

5.0 × 10−15

4 (0.04%)

8.9 × 10−4

2.3 × 10−17

LMM

APOA5

Triglycerides

LoF

42 (0.11%)

2.0 × 10−12

10 (0.11%)

1.1 × 10−2

1.0 × 10−13

LMM

GP9

Mean platelet volumea

Coding

85 (0.22%)

5.2 × 10−11

28 (0.27%)

1.5 × 10−3

3.1 × 10−13

LMM

ANGPTL3

Cholesterol

Coding

175 (0.46%)

3.2 × 10−10

67 (0.62%)

6.8 × 10−4

8.8 × 10−13

LMM

GCK

Glycated haemoglobin

Coding

58 (0.15%)

3.0 × 10−12

9 (0.17%)

8.4 × 10−2

9.3 × 10−13

LMM

TTN

I48 Atrial fibrillation and flutter

LoF

41 (2.38%)/311 (0.8%)b

1.1 × 10−11

12 (1.48%)/132 (0.8%)b

2.8 × 10−2

7.6 × 10−12

FET

COL4A4

R31 Unspecified haematuria

LoF

15 (1.2%)/51 (0.15%)b

1.1 × 10−8

5 (0.47%)/7 (0.05%)b

1.0 × 10−3

1.2 × 10−10

FET

BRCA2

Z40.0 Prophylactic surgery for malignant neoplasm risk-factors

LoF

7 (12.28%)/154 (0.45%)b

1.1 × 10−8

2 (9.52%)/56 (0.38%)b

3.1 × 10−3

1.4 × 10−10

LMM

CST3

Cystatin C

Coding

56 (0.15%)

9.6 × 10−52

   

LMM

SHBG

SHBG

Coding

149 (0.42%)

1.1 × 10−33

   

LMM

LDLR

Non-cancer illness code, self-reported: high cholesterol

Coding

79 (1.54%)/173 (0.49%)b

1.9 × 10−18

   

LMM

SLC45A2

Hair colour: Blonde

Coding

54 (1.16%)/112 (0.31%)b

1.2 × 10−17

   

LMM

STAB1

Median T2star in putamen (right)

LoF

38 (0.4%)

2.1 × 10−14

   

LMM

GP1BB

Mean platelet volumec

Coding

33 (0.08%)

3.0 × 10−12

   

LMM

SMAD6

6 mm weak meridian (right)

LoF

30 (0.11%)

3.1 × 10−11

   

LMM

CRP

C-reactive protein

Coding

66 (0.17%)

6.6 × 10−11

   

LMM

MC1R

Hair colour: Red

Coding

31 (1.75%)/222 (0.57%)b

2.2 × 10−10

   
  1. D45, I48 and R31 refer to ICD-10-CM diagnosis codes, Median T2star is a measurement from a brain MRI, 6 mm weak meridian (right) is from keratometry of the right eye. When multiple phenotypes and/or models (coding, LoF) were significantly associated with a gene, only the lead phenotype and model are shown. When multiple genes were associated with a trait, only the top gene is shown. All results can be found in Supplementary Data 2
  2. LMM linear mixed model, FET Fisher’s exact test, LoF loss of function, HDL high density lipoprotein, LDL low density lipoprotein, SHBG sex hormone binding globulin
  3. aAdditional genes associated with alkaline phosphatase include GPLD1, ASGR1, and ABCB11; with HDL cholesterol include LCAT, CETP, and SCARB1; with LDL direct include PCSK9; with platelet count include MPL and ITGA2B; with urate include SLC2A9; and with mean platelet volume include IQGAP2, GFI1B, and GP1BA
  4. bFor binary traits, the information shown is case n (%)/ctrl n (%)
  5. cAlthough this phenotype was included in the meta-analysis, this particular gene did not have carriers in the HNP cohort
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