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Table 1 Significant large-scale genome-wide associations in patients with severe or critical COVID-19

From: Clinical implications of host genetic variation and susceptibility to severe or critical COVID-19

GWAS study

Study participants

Controls

Genetic ancestry

Genetic cluster(s)

Lead SNP(s) or variant

Gene(s) implicated

Ganna et al.

COVID-19 Host Genetics Initiative (meta-analysis of 46 studies, including the update following data release 6 (www.covid19hg.org)) [24, 33]

COVID-19 patients who required respiratory support or who died as a consequence of COVID-19

N = 9376

Population controls

N = 1,776,645

European, Admixed American, African, Middle Eastern, South Asian and East Asian

1p21.3

rs67579710

i.e. THBS3, MUC1, EFNA1

3p.21.31

rs35508621

LZTFL1, CXCR6

6p21.33

rs111837807

HLA-B, HLA-C

6p21.1

rs1886814

FOXP4

9q34.2

rs912805253

ABO

12q24.13

rs10774679

OAS1, OAS2, OAS3

12q24.33

rs12809318

FBRSL1

16q24.3

rs117169628

i.e. SLC22A31, ACSF3

19p13.3

rs2109069

DPP9

19p13.2

rs74956615

TYK2

21q22.1

rs13050728

IFNAR2, IL10RB

Patients with moderate or severe COVID-19 who required hospitalization

N = 25,027

Population controls

N = 2,836,272

European, Admixed American, African, Middle Eastern, South Asian and East Asian

1p21.3

rs67579710

i.e. THBS3, MUC1, EFNA1

3p.21.31

rs73062389

rs35508621

SLC6A20, SACM1L

LZTFL1, CXCR6

6p21.33

rs111837807

HLA-B, HLA-C

6p21.1

rs1886814

FOXP4

9q34.2

rs912805253

ABO

10q22.3

rs721917

SFTPD

11p15.5

rs35705950

MUC5B

11p13

rs766826

ELF5

12q24.13

rs10774679

OAS1, OAS2, OAS3

12q24.33

rs12809318

FBRSL1

19p13.3

rs2109069

DPP9

19p13.2

rs74956615

TYK2

21q22.1

rs13050728

IFNAR2, IL10RB

Ellinghaus et al.

The Severe COVID-19 GWAS Group [34]

COVID-19 patients hospitalized at the general ward or ICU with respiratory failure, defined as patients requiring oxygen supplementation (non-invasive) or mechanical ventilation. N = 1980

Population controls

N = 2381

European

3p.21.31

rs11385942

SLC6A20, LZTFL1, FYCO1, CXCR6, XCR1 and CCR9

9q34.2

rs657152

ABO

Shelton et al.

23andMe [26]

Patients with self-reported COVID-19 and hospitalization, pneumonia and/or respiratory support

N = 1447

Population controls

N= 796,151

European, Latino, African American

3p.21.31

rs13078854

SLC6A20, LZTFL1, FYCO1, CXCR6, XCR1 and CCR9

Pairo-Castineira et al.

GenOMICC/ISARIC [23]

COVID-19 patients requiring continuous cardiorespiratory monitoring, in high-dependency or intensive care units

N = 2244 (primary analysis on data from 1676 individuals of European ancestry)

Ancestry-matched population controls

N = 8380

European, South Asian, African, East Asian

3p.21.31

rs73064425

LZTFL1, CXCR6, FYCO1, CCR3

6p22.1

rs9380142

HLA-Ga

6p21.33

rs143334143

CCHCR1a

6p21.32

rs3131294

NOTCH4a

12q24.13

rs10735079

OAS1, OAS2, OAS3

19p13.3

rs2109069

DPP9

19p13.2

rs74956615

TYK2

21q22.1

rs2236757

IFNAR2

Andolfo et al.b [28]

Hospitalized COVID-19 patients

N = 7970

Population controls

N = 902,088

European

21q22.1

rs13050728

IFNAR2

21q22.3

rs3787946

MX1, TMPRSS2

Kousanathos et al.c

GenOMICC/ISARIC [35]

COVID-19 patients requiring continuous cardiorespiratory monitoring, in high-dependency or intensive care units

N = 7491

Ancestry-matched population controls

N = 48,400 controls

European, South Asian, African, East Asian

1p21.3

rs114301457, rs7528026, rs41264915

MUC1, THBS3, EFNA4, TRIM46

2p16.1

rs1123573

BCL11A

3p.21.31

rs2271616, rs73064425

LZTFL1, CXCR6, CCR9, XCR1

6p21.33

rs9271609

HLA-G, HLA-DRB1, HLA-DQA1

11p13

rs61882275

ELF5

12.q24.33

rs56106917

FBRLS1

13q34

rs9577175

ATP11A

19p13.3r

s12610495

DPP9

19p13.2

rs34536443

TYK2

21q22.1

rs17860115, rs8178521

IFNAR2, IL10RB, IFNAR1

  1. aThe authors state that these variants are located in a region of chromosome 6 for which population stratification is difficult to control (the major histocompatibility complex) and did not replicate in a meta-analysis of data from other studies
  2. bThe authors have conducted a meta-analysis on existing data from the COVID-19 Human Genetic Effort using summary statistics, with a focus on chromosome 21. The investigated 21q22.3 locus did not harbour genome-wide significant eQTLs (p-value ≤ 5 × 10−8); however, 5 common SNPs in this locus (p-value ≤ 1 × 10−5) were validated in other cohorts of hospitalized COVID-19 patients
  3. cThis study involved critical COVID-19 patients that were recruited to the GenOMICC study, of which 1339 had already been included in a primary analysis published previously [23]
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Genome Medicine

ISSN: 1756-994X

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