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A GWAS in the pandemic epicenter highlights severe COVID-19 risk locus introgressed by Neanderthals

Large GWAS indicated that genetic factors influence the response to #SARSCoV2. However, sex, age, concomitant diseases, differences in ancestry, and uneven exposure to the virus impacted the interpretation of data. We aimed to perform a GWAS of #COVID19 outcome in a homogenous population who experienced a high exposure to the virus and with a known infection status. We recruited inhabitants of Bergamo province -that in spring 2020 was the epicenter of the SARS-Cov-2 pandemic in Europe- via an online questionnaire followed by personal interviews. Cases and controls were matched by age, sex and risk factors. We genotyped 1195 individuals and replicated the association at the 3p21.31 locus with severity, but with a stronger effect size that further increased in gravely-ill patients. Transcriptome-wide association study highlighted eQTLs for LZTFL1 and CCR9. We also identified 17 loci not previously reported, suggestive for an association with either COVID-19 severity or susceptibility.




Highlights


  • •The Neanderthal haplotype is the major genetic risk factor for severe COVID-19

  • •The effect size of the locus further increases in most severe patients.

  • •The risk haplotype likely influences the expression of LZTFL1 and CCR9.



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