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

Matteo Breno; Marina Noris; Nadia Rubis; Aneliya Ilieva Parvanova; Davide Martinetti; Sara Gamba; Lucia Liguori; Caterina Mele; Rossella Piras; Silvia Orisio; Elisabetta Valoti; Marta Alberti; Olimpia Diadei; Elena Bresin; Miriam Rigoldi; Silvia Prandini; Tiziano Gamba; Nadia Stucchi; Fabiola Carrara; Erica Daina; Ariela Benigni; Giuseppe Remuzzi; ORIGIN study group

doi:10.1016/j.isci.2023.107629

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

iScience. 2023 Aug 16;26(10):107629. doi: 10.1016/j.isci.2023.107629. eCollection 2023 Oct 20.

Authors

Matteo Breno¹, Marina Noris¹, Nadia Rubis¹, Aneliya Ilieva Parvanova¹, Davide Martinetti¹, Sara Gamba¹, Lucia Liguori¹, Caterina Mele¹, Rossella Piras¹, Silvia Orisio¹, Elisabetta Valoti¹, Marta Alberti¹, Olimpia Diadei¹, Elena Bresin¹, Miriam Rigoldi¹, Silvia Prandini¹, Tiziano Gamba¹, Nadia Stucchi¹, Fabiola Carrara¹, Erica Daina¹, Ariela Benigni¹, Giuseppe Remuzzi¹; ORIGIN study group

Affiliation

¹ Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Clinical Research Center for Rare Diseases Aldo e Cele Daccò and Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy.

Abstract

Large GWAS indicated that genetic factors influence the response to SARS-CoV-2. 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 COVID-19 outcome in a homogeneous 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.

Keywords: Genomics; Public health; Respiratory medicine; Virology.