Abstract
<title>Abstract</title> <p>The marked interindividual variability in COVID-19 clinical manifestations suggests that host genetic variation contributes to disease severity. To investigate host genetic variants associated with COVID-19 severity, we conducted an exploratory genome-wide association study (GWAS) in an admixed Brazilian cohort. A subset of 96 individuals was selected from a larger clinical cohort, of whom 92 underwent high-density SNP genotyping. After genotype quality control and identity-by-descent filtering, 73 unrelated individuals remained for genome-wide association analyses. The strongest association was identified at the PASD1 locus (rs56035326), where the minor allele (T) was significantly more frequent in mild than in severe COVID-19 cases (MAF = 0.54 vs. 0.05; p = 4.42 × 10⁻⁸), remaining significant after false discovery rate correction. Additional suggestive associations were observed in DNAH9, ADRA1A, and C1ORF132 but did not remain significant after correction for multiple testing. To our knowledge, this study provides the first evidence implicating PASD1 genetic variation in COVID-19 severity, providing a basis for future replication and functional studies investigating the biological mechanisms underlying severe COVID-19, particularly in admixed populations.</p>