Systematic characterization of the genetic architecture of acute COVID-19 and its long-term sequelae in the German National Pandemic Cohort (NAPKON)
1 Institute of Psychiatry and Psychotherapy, University of Bonn, School of Medicine & University Hospital Bonn
2 Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn
3 Hannover Unified Biobank (HUB), Hannover Medical School
Large-scale host genetic analyses are integral for understanding the genetic architecture of COVID-19 and its post-acute sequelae. While genetic risk variants have been identified for severe COVID-19, the genetic basis underlying the development of Post COVID, characterized by predominant neuropsychiatric symptoms, remains largely unknown. The National Pandemic Cohort Network (NAPKON), launched in July 2020 under the German Network of University Medicine (NUM), encompasses over 5,000 participants across the healthcare spectrum. Whole exome sequencing (WES) within this cohort offers a cost-efficient and comprehensive strategy for uncovering functionally relevant rare variants associated with COVID-19 and its neuropsychiatric manifestations and will complement existing multi-omics data for NAPKON participants, including genotyping and cytokine measurements. This initiative aims to identify rare and common host genetic factors implicated in diverse COVID-19-related phenotypes, including Post COVID symptoms such as neurocognitive impairment, fatigue, depression, and anxiety. To achieve this, we will conduct classical statistical analyses (e.g., single variant association, gene burden testing) and integrate array-based genotypes to combine variants across the entire allelic spectrum e.g. in polygenic risk scores. Deep phenotyping information will facilitate subgroup analyses, while transcriptomics, proteomics, and epigenomics data will help to functionally interpret risk variants. Initial results will be presented at the conference. This project bridges the gap from variant identification to the pathophysiological understanding of neuropsychiatric manifestations of Post COVID. It provides significant value to NAPKON/NUM efforts and the fields of host genetics/functional genomics by generating one of the few highly visible and reusable large-scale WES datasets in Germany.