In:
PLOS Genetics, Public Library of Science (PLoS), Vol. 18, No. 4 ( 2022-4-28), p. e1010113-
Abstract:
The study aims to determine the shared genetic architecture between COVID-19 severity with existing medical conditions using electronic health record (EHR) data. We conducted a Phenome-Wide Association Study (PheWAS) of genetic variants associated with critical illness (n = 35) or hospitalization (n = 42) due to severe COVID-19 using genome-wide association summary data from the Host Genetics Initiative. PheWAS analysis was performed using genotype-phenotype data from the Veterans Affairs Million Veteran Program (MVP). Phenotypes were defined by International Classification of Diseases (ICD) codes mapped to clinically relevant groups using published PheWAS methods. Among 658,582 Veterans, variants associated with severe COVID-19 were tested for association across 1,559 phenotypes. Variants at the ABO locus (rs495828, rs505922) associated with the largest number of phenotypes (n rs495828 = 53 and n rs505922 = 59); strongest association with venous embolism, odds ratio (OR rs495828 1.33 (p = 1.32 x 10 −199 ), and thrombosis OR rs505922 1.33, p = 2.2 x10 -265 . Among 67 respiratory conditions tested, 11 had significant associations including MUC5B locus (rs35705950) with increased risk of idiopathic fibrosing alveolitis OR 2.83, p = 4.12 × 10 −191 ; CRHR1 ( rs61667602) associated with reduced risk of pulmonary fibrosis, OR 0.84, p = 2.26× 10 −12 . The TYK2 locus (rs11085727) associated with reduced risk for autoimmune conditions, e.g., psoriasis OR 0.88, p = 6.48 x10 -23 , lupus OR 0.84, p = 3.97 x 10 −06 . PheWAS stratified by ancestry demonstrated differences in genotype-phenotype associations. LMNA (rs581342) associated with neutropenia OR 1.29 p = 4.1 x 10 −13 among Veterans of African and Hispanic ancestry but not European. Overall, we observed a shared genetic architecture between COVID-19 severity and conditions related to underlying risk factors for severe and poor COVID-19 outcomes. Differing associations between genotype-phenotype across ancestries may inform heterogenous outcomes observed with COVID-19. Divergent associations between risk for severe COVID-19 with autoimmune inflammatory conditions both respiratory and non-respiratory highlights the shared pathways and fine balance of immune host response and autoimmunity and caution required when considering treatment targets.
Type of Medium:
Online Resource
ISSN:
1553-7404
DOI:
10.1371/journal.pgen.1010113
DOI:
10.1371/journal.pgen.1010113.g001
DOI:
10.1371/journal.pgen.1010113.g002
DOI:
10.1371/journal.pgen.1010113.g003
DOI:
10.1371/journal.pgen.1010113.t001
DOI:
10.1371/journal.pgen.1010113.t002
DOI:
10.1371/journal.pgen.1010113.s001
DOI:
10.1371/journal.pgen.1010113.s002
DOI:
10.1371/journal.pgen.1010113.s003
DOI:
10.1371/journal.pgen.1010113.s004
DOI:
10.1371/journal.pgen.1010113.s005
DOI:
10.1371/journal.pgen.1010113.s006
DOI:
10.1371/journal.pgen.1010113.s007
DOI:
10.1371/journal.pgen.1010113.s008
DOI:
10.1371/journal.pgen.1010113.s009
DOI:
10.1371/journal.pgen.1010113.s010
DOI:
10.1371/journal.pgen.1010113.s011
DOI:
10.1371/journal.pgen.1010113.s012
DOI:
10.1371/journal.pgen.1010113.s013
DOI:
10.1371/journal.pgen.1010113.s014
DOI:
10.1371/journal.pgen.1010113.r001
DOI:
10.1371/journal.pgen.1010113.r002
DOI:
10.1371/journal.pgen.1010113.r003
DOI:
10.1371/journal.pgen.1010113.r004
DOI:
10.1371/journal.pgen.1010113.r005
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2186725-2
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