Shared genetic architecture and causal relationship between the age at first sex and COVID-19: A large-scale cross-trait analysis (preprint)

ABSTRACT

COVID-19 is genetically associated with numerous immune disorders, and young age at first intercourse (AFS) may lead to early activation of innate immunity. However, the genetic overlap between COVID-19 and AFS remains undetermined. Here we perform a large-scale cross-trait analysis to investigate their shared genetic etiology and causal relationship. An overall negative genetic correlation between the AFS and three COVID-19 traits was observed. We further identified 186, 221, and 213 shared genetic loci for AFS-COVID-19 infection, hospitalization, and severity, respectively. Among these shared loci, those closest to the genes CADM2, and ARPC1B showed the strongest signals. Our post-GWAS functional analysis revealed that the shared mapped genes were mainly involved in neural genesis and development within several brain structures. Finally, bidirectional Mendelian randomization (MR) results showed that earlier sexual debut may increase the risk of SARS-CoV-2 infection, hospitalization, and severity.