5 research outputs found
Mapping the human genetic architecture of COVID-19
- Author
- Abdelrazik M.
- Abdullah T.
- Abe R.
- Abe S.
- Abecasis G. R.
- Abel L.
- Abernathy C.
- Abraheem A.
- Abul-Husn N. S.
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- Zitter L.
- Zlatopolsky M.
- Zoller H.
- Zollner S.
- Zongo O.
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- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2021
- Field of study
Get PDFThe genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease
Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality
- Author
- Alarcon-Riquelme M. E.
- Amitrano S.
- Asselta R.
- Banales J. M.
- Bernardo D.
- Bouysran Y.
- Bujanda L.
- Buti M.
- Butler-Laporte G.
- Cordioli M.
- Darcis G.
- Degenhardt F.
- Duga S.
- Ellinghaus D.
- Fava F.
- Fernandez-Cadenas I.
- Franke A.
- Frithiof R.
- Ganna A.
- Garcia F.
- Gen F.
- Holter J. C.
- Hov J. R.
- Karlsen T. H.
- Khan A.
- Kiryluk K.
- Ludwig K. U.
- Martinez-Bueno M.
- Maya-Miles D.
- Migeotte I.
- Nafria-Jimenez B.
- Nakanishi T.
- Niemi M. E. K.
- Palom A.
- Pereira A. C.
- Pigazzini S.
- Planas A. M.
- Prati D.
- Rahmouni S.
- Renieri A.
- Richards J. B.
- Rolker S.
- Romero-Gomez M.
- Schulte E. C.
- Spinner C. D.
- Tato L. R.
- Valenti L.
- Zeberg H.
- Publication venue
- 'American Society for Clinical Investigation'
- Publication date
- 01/01/2021
- Field of study
No full textBACKGROUND. There is considerable variability in COVID-19 outcomes among younger adults, and some of this variation may be due to genetic predisposition. METHODS. We combined individual level data from 13,888 COVID-19 patients (n = 7185 hospitalized) from 17 cohorts in 9 countries to assess the association of the major common COVID-19 genetic risk factor (chromosome 3 locus tagged by rs10490770) with mortality, COVID-19-related complications, and laboratory values. We next performed metaanalyses using FinnGen and the Columbia University COVID-19 Biobank. RESULTS. We found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (HR, 1.4; 95% CI, 1.2-1.7). Risk allele carriers had increased odds of several COVID-19 complications: severe respiratory failure (OR, 2.1; 95% CI, 1.6-2.6), venous thromboembolism (OR, 1.7; 95% CI, 1.2-2.4), and hepatic injury (OR, 1.5; 95% CI, 1.2-2.0). Risk allele carriers age 60 years and younger had higher odds of death or severe respiratory failure (OR, 2.7; 95% CI, 1.8-3.9) compared with those of more than 60 years (OR, 1.5; 95% CI, 1.2-1.8; interaction, P = 0.038). Among individuals 60 years and younger who died or experienced severe respiratory failure, 32.3% were risk-variant carriers compared with 13.9% of those not experiencing these outcomes. This risk variant improved the prediction of death or severe respiratory failure similarly to, or better than, most established clinical risk factors. CONCLUSIONS. The major common COVID-19 genetic risk factor is associated with increased risks of morbidity and mortality, which are more pronounced among individuals 60 years or younger. The effect was similar in magnitude and more common than most established clinical risk factors, suggesting potential implications for future clinical risk management
Novel genes and sex differences in COVID-19 severity.
- Author
- Aguado J.
- Aguilar C.
- Aguilera-Albesa S.
- Alarcón-Riquelme M.
- Almadana V.
- Almoguera B.
- Alvarez N.
- Amitrano S.
- Andreu-Bernabeu Á.
- Arana-Arri E.
- Arango C.
- Arranz M.
- Artiga M.
- Asselta R.
- Ayuso C.
- Banales J.
- Baptista-Rosas R.
- Barreda-Sánchez M.
- Belhassen-Garcia M.
- Bernardo D.
- Bezerra J.
- Bezerra M.
- Boada M.
- Boix-Palop L.
- Bouysran Y.
- Brion M.
- Brugada R.
- Bujanda L.
- Bustos M.
- Buti M.
- Butler-Laporte G.
- Calderón E.
- Carbonell C.
- Carmen Fariñas M.
- Carracedo A.
- Castano L.
- Castelao J.
- Ceballos F.
- Conde-Vicente R.
- Cordero-Lorenzana M.
- Cortes-Sanchez J.
- Corton M.
- Cruz R.
- Darcis G.
- Darnaude M.
- De Martino-Rodríguez A.
- de Rojas I.
- Degenhardt F.
- del Campo-Pérez V.
- Diaz de Bustamante A.
- Diz-de Almeida S.
- Domínguez-Garrido E.
- Duga S.
- Eiros R.
- Ellinghaus D.
- Estigarribia Sanabria G.
- Fava F.
- Fernandes M.
- Fernández-Cadenas I.
- Fernández-Robelo U.
- Fernández-Rodríguez A.
- Fernández-Villa T.
- Flores C.
- Franke A.
- Frithiof R.
- Gago-Domínguez M.
- Ganna A.
- Garcia F.
- Gil-Fournier B.
- Gonzalez Bernaldo de Quirós F.
- González Álvarez B.
- González-Montelongo R.
- González-Neira A.
- González-Peñas J.
- Guillen-Navarro E.
- Gutiérrez-Bautista J.
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- Herrero M.
- Herrero-Gonzalez A.
- Holter J.
- Hov J.
- Jimenez-Sousa M.
- Karlsen T.
- Lapunzina P.
- Lattig M.
- Liger Borja A.
- Lopez-Rodriguez R.
- Lorenzo-Salazar J.
- Luchessi A.
- Ludwig K.
- López de Heredia M.
- Mancebo E.
- Martinez-Lopez I.
- Martinez-Nieto O.
- Martinez-Perez A.
- Martinez-Resendez M.
- Martín V.
- Martín-López C.
- Martínez-Bueno M.
- Maya-Miles D.
- Mazzeu J.
- Merayo Macías E.
- Migeotte I.
- Minguez P.
- Moreno Cuerda V.
- Nafría-Jiménez B.
- Nakanishi T.
- Nevado J.
- Oliveira S.
- Ortega-Paino E.
- Palom A.
- Parellada M.
- Paz-Artal E.
- Pereira A.
- Perez P.
- Perucho T.
- Pigazzini S.
- Pinsach-Abuin M.
- Pita G.
- Planas A.
- Pompa-Mera E.
- Porras-Hurtado G.
- Prati D.
- Pujol A.
- Pérez-Matute P.
- Pérez-Tomás M.
- Quintela I.
- Rahmouni S.
- Ramiro León S.
- Real L.
- Renieri A.
- Resino S.
- Riancho J.
- Richards B.
- Roade L.
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- Rodríguez-Ruiz E.
- Rojas-Martinez A.
- Rolker S.
- Romero-Gómez M.
- Ruiz Cabello F.
- Ruiz A.
- Ruiz-Hornillos J.
- Ryan P.
- Santos N.
- Schulte E.
- Sevilla Porras M.
- Silbiger V.
- Soria J.
- Souto J.
- Spinner C.
- Sánchez-Juan P.
- Tamayo E.
- Tamayo-Velasco A.
- Taracido-Fernandez J.
- Tenorio Castaño J.
- Teper A.
- Torres-Tobar L.
- Urioste M.
- Valencia-Ramos J.
- Valenti L.
- Yáñez Z.
- Zarate R.
- Zeberg H.
- Publication venue
- 'Oxford University Press (OUP)'
- Publication date
- 01/01/2022
- Field of study
Get PDFHere we describe the results of a genome-wide study conducted in 11 939 COVID-19 positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (p < 5x10-8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (p = 1.3x10-22 and p = 8.1x10-12, respectively), and for variants in 9q21.32 near TLE1 only among females (p = 4.4x10-8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (p = 2.7x10-8) and ARHGAP33 (p = 1.3x10-8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, p = 4.1x10-8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥ 60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided
A second update on mapping the human genetic architecture of COVID-19
- Author
- Abd Elghafar MS
- Abdel-Aziz M
- Abdelrazik M
- Abdullah MS
- Abe R
- Abe S
- Abel L
- Abel L
- Abernathy C
- Abraham R
- Abraheem A
- Abu Alragheb BO
- Abulail JA
- Acklery A
- Acosta-Herrera M
- Adachi T
- Adachi Y
- Adam R
- Adams C
- Adams K
- Adams N
- Adanini O
- Afifi N
- Afilalo J
- Afilalo M
- Afolabi D
- Afrasiabi Z
- Afset JE
- Agasou A
- Aghemo A
- Agravante K
- Agrawal A
- Agrawal S
- Aguado JM
- Aguilar C
- Aguilar SEV
- Aguilar-Salinas CA
- Aguilera-Albesa S
- Agüero D
- Ahmad HF
- Ahmad N
- Ahmadhaider N
- Ahmed A
- Ahmed C
- Ahram M
- Ai M
- Ain Q
- Aitkin E
- Akeroyd L
- Akhtar MN
- Akinkugbe O
- Al-Ani A
- Al-Ja’afreh MM
- Al-Kadash A
- Al-Kasasbeh MM
- Al-Moasseb H
- Al-Muftah W
- Al-Sarraj Y
- Alamer LM
- Alasdair F
- Alawneh FM
- Alawneh LM
- Albaiceta GM
- Albano G
- Albillos A
- Albrecht W
- Aldridge J
- Alexander P
- Alfonso J
- Alhousani TN
- Ali A
- Ali HH
- Ali IAM
- Ali S
- Aliberti S
- ALjalamdeh M
- Allan A
- Allan E
- Allan J
- Alldis Z
- Allen L
- Allen M
- Allen S
- Allen U
- Allibone S
- Allison KS
- Allouzy SK
- Ally SM
- Almadana V
- Almaden-Boyle C
- Almoguera B
- Alpuche-Aranda C
- AlRawashdeh TJ
- Alsafadi DB
- Alshaer W
- Alsoub FS
- Altabaibeh A
- Alvarez N
- Alvaro A
- Alzuraiqi MR
- Amamio M
- Aman NF
- Amin V
- Amiya S
- Ampuero J
- Anan R
- Anastasescu E
- Andersen S
- Anderson J
- Anderson M
- Anderson P
- Anderson S
- Anderson S
- Anderson T
- Ando A
- Andrade V
- Andreou P
- Andreu-Bernabeu Á
- Andrew A
- Andrew B
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- Andrews J
- Andrews S
- Andrews SJ
- Angelini C
- Ansari AI
- Antcliffe D
- Antoine P
- Antony S
- Anumakonda V
- Anwer M
- Anzai T
- Apetri E
- Aquino M
- Aquino-Gálvez A
- Arai D
- Arakelyan A
- Arana-Arri E
- Arana-Arri E
- Arango C
- Aravindan L
- Arbane G
- Archer K
- Arden T
- Arias SS
- Arif S
- Arimura K
- Armistead J
- Armstrong D
- Armstrong J
- Armstrong L
- Armstrong R
- Arning N
- Arnoldo S
- Arnott A
- Arora J
- Arora M
- Arranz MJ
- Arranz MJ
- Arribas-Rodriguez E
- Artiga M-J
- Arumugam P
- Asakura T
- Asano K
- Aschard H
- Ashby K
- Ashok SR
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- Ashton L
- Asimakopoulos A
- Aslibekyan S
- Asselta R
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- Atayeva N
- Athanasiou L
- Atkinson EG
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- Auld D
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- Auton A
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- Awasthi S
- Ayers A
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- Aziz F
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- Azuma M
- Azuure C
- Azzolini E
- Baba R
- Baba T
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- Badal B
- Badalamenti S
- Baddeley A
- Badia JR
- Badji RM
- Bafitis V
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- Baines D
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- Bakthavatsalam D
- Balaconis MK
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- Banales JM
- Banasik K
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- Baptista D
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- Yeung RSM
- Yi X
- Yonekawa A
- Yoo S
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- Yoshida S
- Yoshida T
- Yoshihara T
- Yoshiya K
- Yoshiyama T
- Young M
- Yue F
- Yun N
- Yáñez CE
- Yáñez Z
- Zainulabid UA
- Zainy T
- Zak A
- Zaki A
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- Zamudio IPM
- Zanella A
- Zapata-Contreras D
- Zapatamartinez M
- Zarate R
- Zarei N
- Zavaleta DAF
- Zawadzki P
- Zawati MH
- Zborowski AC
- Zeberg H
- Zechner M
- Zhang Q
- Zhao X
- Zheng C
- Zheng T
- Zhlawi HJ
- Zhlawi MWJ
- Zholdybayeva E
- Zhou W
- Zhu W
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- Zongo O
- Zorloni C
- Zuñiga-Pacheco P
- Zárate RN
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- Álvarez BG
- Ávila-Arcos MA
- Ávila-Arcos MC
- Özer O
- Überla K
- Þorsteinsdóttir U
- Publication venue
- Nature Research
- Publication date
- 21/06/2023
- Field of study
Get PDFMapping the human genetic architecture of COVID-19
- Author
- Abdelrazik M
- Abdullah T
- Abe R
- Abe S
- Abecasis GR
- Abel L
- Abernathy C
- Abraheem A
- Abul-Husn NS
- Acosta-Herrera M
- Acquilini D
- Acquilini D
- Adachi T
- Adachi Y
- Adams C
- Adams K
- Adanini O
- Adeleye O
- Adeniji K
- Adra D
- Afifi N
- Afilalo J
- Afilalo M
- Afolabi D
- Afrasiabi Z
- Afset JE
- Agasou A
- Aghemo A
- Agranoff D
- Agrawal S
- Aguirre LA
- Agwuh K
- Ahmad HF
- Ahmad N
- Ahmed A
- Ahmed C
- Ahmed KA
- Ai M
- Ail D
- Akeroyd L
- Akhtar MN
- Akhtar S
- Akinkugbe O
- Aksentijevich A
- Al Thani A
- Al-Muftah W
- Al-Sarraj Y
- Alarcon C
- Alarcon-Riquelme ME
- Alasdair F
- Alaverdian D
- Alavere H
- Albertos R
- Albillos A
- Albrecht W
- Albrich W
- Albrich WC
- Aldera EL
- Aldridge J
- Alegria A
- Alex B
- Alexander P
- Alfonso J
- Algera AG
- Ali A
- Ali IMA
- Ali S
- Aliberti S
- Allan A
- Allan E
- Allan J
- Alldis Z
- Allen L
- Allen S
- Allibone S
- Allison KS
- Allos R
- Ally SM
- Almaden-Boyle C
- Altabaibeh A
- Altmueller J
- Alvaro A
- Amar D
- Amin V
- Amitrano S
- Amiya S
- Ampuero J
- Anan R
- Anania S
- Anastasescu E
- Anderson F
- Anderson J
- Anderson M
- Anderson P
- Anderson S
- Anderson S
- Anderson T
- Ando A
- Andolfo I
- Andrade V
- Andretta F
- Andreucci E
- Andreucci E
- Andrew A
- Andrew B
- Andrew G
- Andrews E
- Andrews SJ
- Andrews SJ
- Andrews SJ
- Andrews SJ
- Andrikopoulos P
- Anedda F
- Aneli S
- Anemoli V
- Angelini C
- Angus B
- Annis A
- Antcliffe D
- Antinori A
- Antoni MD
- Anumakonda V
- Anwar M
- Anzai T
- Apetri E
- Arai D
- Arana E
- Arbane G
- Archer K
- Arciero E
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- Arif S
- Arimura K
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- Armstrong JA
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- Armstrong R
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- Arora J
- Artuso R
- Arumugam P
- Asakura T
- Asano K
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- Ascolillo S
- Ashish A
- Ashley E
- Ashraf S
- Ashraf S
- Ashton L
- Ashworth M
- Asiimwe IG
- Aslibekyan S
- Asselta R
- Atanasovska B
- Atkinson D
- Atkinson EG
- Attwood B
- Aucella F
- Augustin M
- Auld D
- Auld F
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- Awano N
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- Azuma M
- Azuure C
- Azzolini E
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- Badalamenti S
- Badia JR
- Badji RM
- Bahmer T
- Baikady RR
- Baillie JK
- Baillie JK
- Baillie JK
- Baillie JK
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- Bakthavatsalam D
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- Baldassarri M
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- Bandla N
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- Below JE
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- Beranova E
- Bercades G
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- Berger MM
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- Bergomi P
- Berkowitz N
- Bernardo D
- Bernasconi A
- Bernatoniene J
- Berridge J
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- Bettini LR
- Beudel M
- Bevan E
- Bewley J
- Bhardwaj N
- Bhatia N
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- Blakemore H
- Blanco-Grau A
- Blasi F
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- Blay N
- Blow S
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- Boada M
- Board S
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- Bocciolone M
- Bochud M
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- Bochud PY
- Bochud PY
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- Brimfield L
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- Brusco A
- Bruttini M
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- Bujanda L
- Bulik CM
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- Bullock K
- Bulteel N
- Bunni L
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- Burn I
- Burnett C
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- Burtenshaw A
- Burtenshaw A
- Burton M
- Busani S
- Busson A
- Bussotti M
- Bustamante C
- Butcher D
- Buti M
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- Butler-Laporte G
- Butler-Laporte G
- Butler-Laporte G
- Butler-Laporte G
- Butte MJ
- Butterworth AS
- Butterworth-Cowin N
- Button H
- Buxbaum JD
- Buxbaum JD
- Buxbaum JD
- Byun J
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- Cabrelli L
- Caceres M
- Cadilla CL
- Cagova L
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- Calderon EJ
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- Carlucci N
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- zu Bentrup FM
- Zucchi P
- Zwinderman AHK
- Zyndorf M
- Publication venue
- Publication date
- 01/01/2021
- Field of study
Get PDFThe genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3,4,5,6,7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease
