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10.1101/2021.05.18.21257396 http://scihub22266oqcxt.onion/10.1101/2021.05.18.21257396 34642702!8509103!34642702     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=34642702&cmd=llinks): Failed to open stream: HTTP request failed! 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A Phenome-Wide Association Study of genes associated with COVID-19 severity reveals shared genetics with complex diseases in the Million Veteran Program |pdf=|usr=}}{{34642702}} gab.com Text A Phenome-Wide Association Study of genes associated with COVID-19 severity reveals shared genetics with complex diseases in the Million Veteran Program JO: medRxiv http://www.kidney.de/pget.php?&tw=1&pmid=34642702 #FOAvip 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 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 (ORrs495828 1.33 (p=1.32 x 10(-199)), and thrombosis OR(rs505922) 1.33, p=2.2 x 10(-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 x 10(-191); CRHR1 (rs61667602) associated with reduced risk of pulmonary fibrosis, OR 0.84, p=2.26 x 10(-12). The TYK2 locus (rs11085727) associated with reduced risk for autoimmune conditions, e.g., psoriasis OR 0.88, p=6.48 x 10(-23), lupus OR 0.84, p=3.97 x 10(-06). PheWAS stratified by genetic ancestry demonstrated differences in genotype-phenotype associations across ancestry. LMNA (rs581342) associated with neutropenia OR 1.29 p=4.1 x 10(-13) among Veterans of African 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. Twit Text FOAVip A Phenome-Wide Association Study of genes associated with COVID-19 severity reveals shared genetics with complex diseases in the Million Veteran Program ????medRxiv http://www.kidney.de/pget.php?&tw=1&pmid=34642702 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=34642702 #FOAvip English Wikipedia <ref>{{Cite pmid|34642702}}</ref> A Phenome-Wide Association Study of genes associated with COVID-19 severity reveals shared genetics with complex diseases in the Million Veteran Program #MMPMID34642702 Verma A; Tsao N; Thomann L; Ho YL; Iyengar S; Luoh SW; Carr R; Crawford D; Efird JT; Huffman J; Hung A; Ivey K; Levin M; Lynch J; Natarajan P; Pyarajan S; Bick A; Costa L; Genovese G; Hauger R; Madduri R; Pathak G; Polimanti R; Voight B; Vujkovic M; Zekavat M; Zhao H; Ritchie MD; Chang KM; Cho K; Casas JP; Tsao PS; Gaziano JM; O'Donnell C; Damrauer S; Liao K medRxiv 2021[Oct]; ä (ä): ä PMID34642702show ga 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 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 (ORrs495828 1.33 (p=1.32 x 10(-199)), and thrombosis OR(rs505922) 1.33, p=2.2 x 10(-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 x 10(-191); CRHR1 (rs61667602) associated with reduced risk of pulmonary fibrosis, OR 0.84, p=2.26 x 10(-12). The TYK2 locus (rs11085727) associated with reduced risk for autoimmune conditions, e.g., psoriasis OR 0.88, p=6.48 x 10(-23), lupus OR 0.84, p=3.97 x 10(-06). PheWAS stratified by genetic ancestry demonstrated differences in genotype-phenotype associations across ancestry. LMNA (rs581342) associated with neutropenia OR 1.29 p=4.1 x 10(-13) among Veterans of African 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. äA Phenome-Wide Association Study of genes associated with COVID-19 sev(epmc).pdf DeepDyve Pubget Overpricing