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Source: COVID-19-Genetics  Dec 14, 2021  2 years, 4 months, 3 days, 22 hours, 24 minutes ago

Duke University’s COVID-19 Genetics And Phenotype Study Discovers Alternate Associations With SARS-CoV-2 Risk Loci.

Duke University’s COVID-19 Genetics And Phenotype Study Discovers Alternate Associations With SARS-CoV-2 Risk Loci.
Source: COVID-19-Genetics  Dec 14, 2021  2 years, 4 months, 3 days, 22 hours, 24 minutes ago
COVID-19-Genetics: Researchers from Duke Molecular Physiology Institute-North Carolina, USA, Duke University Department of Medicine-North Carolina, USA and Duke Clinical Research Institute-North Carolina, USA have in a new study discovered alternate associations with SARS-CoV-2 risk loci.


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Genetic loci associated with risk of severe COVID-19 infection were identified and it was found that individuals with complicated COVID-19 infections often have multiple comorbidities.
 
The study team wanted to identify known and unidentified comorbidities associated with genetic loci linked to risk of severe COVID-19 infection.
 
A detailed Phenome Wide Association Study (PheWAS) was conducted in 247,448 unrelated, white individuals from the UK Biobank to test the association of 1,402 unique phenotypes with ten genome-wide significant severe-COVID risk single nucleotide polymorphisms (SNP) identified from prior studies. A validation PheWAS was conducted in 2,247 white individuals from the CATHGEN.
 
The study findings showed that four of the ten tested genetic loci showed significant phenotypic associations in UK Biobank after FDR adjustment.
 
Vascular dementia significantly associated with rs7271165 near TMEM65 on 8q24.13 in individuals with the C risk allele (OR 5.66 [95% CI 2.21-11.85], q=0.049).
 
The study findings also identified 40 novel phenotype associations with rs657152 on 9q34.2 coinciding with the ABO gene with individuals with the A COVID risk allele having higher odds of heart failure (OR 1.09 [95% CI 1.03-1.14], q=0.004), diabetes mellitus (OR 1.05 [95% CI 1.02-1.07], q=0.004) and hypercholesterolemia (OR 1.04 [95% CI 1.02-1.06], q=6.3x10-5).
 
Eight phenotypes associated with rs1819040 near KANSL1 on 17q21.31 in individuals with the A risk allele including atrial fibrillation and flutter (OR 1.07 [95% CI 1.04-1.10], q=0.0084) and pulmonary fibrosis (OR 0.80 [95% CI 0.71-0.89], q=0.035).
 
Ten novel phenotypic associations were identified in association with rs74956615 on 19p13.2 near the TYK2 gene including individuals with the A COVID risk allele having lower odds of psoriatic arthropathy (OR 0.31 [95% CI 0.20-0.47], q=4.5x10-5), rheumatoid arthritis (OR 0.83 [95% CI 0.64-0.83], p=1.4x10-6) and thyrotoxicosis with or without goiter (OR 0.77 [95% CI 0.68-0.87], p-6.9x10-5).
 
Two associations for rs1819040 (KANSL1) and seven associations for rs74956615 (TYK2) validated in CATHGEN.
 
The study findings identified novel phenotypic associations with risk alleles for severe COVID-19 infection. Interestingly, the ABO locus was associated with comorbidities that are also