# Natural selection exerted by historical coronavirus epidemic(s): comparative genetic analysis in China Kadoorie Biobank and UK Biobank

## TL;DR

The study finds evidence that ancient coronavirus epidemics in East Asia led to genetic changes that can still be seen in modern populations.

## Contribution

The study uses large-scale genetic data from East Asia and the UK to show evidence of historical coronavirus-driven selection in East Asians but not in Europeans.

## Key findings

- Regions of long-range linkage disequilibrium were enriched for coronavirus VIPs in the China Kadoorie Biobank but not in the UK Biobank.
- Selection-scan methods like saltiLASSI confirmed the enrichment of VIPs in East Asian populations.
- SARS-CoV-2 GWAS signals showed no population-specific selection patterns, consistent with being a novel virus.

## Abstract

Pathogens have been one of the primary sources of natural selection affecting modern humans. The footprints of historical selection events – “selective sweeps”– can be detected in the genomes of present-day individuals. Previous analyses of 629 samples from the 1000 Genomes Project suggested that an ancient coronavirus epidemic ~ 20,000 years ago drove multiple selective sweeps in the ancestors of present-day East Asians, but not in other worldwide populations.

Using a much larger genetic dataset of 76,719 unrelated individuals from each of the China Kadoorie Biobank (CKB) and UK Biobank (UKB) to identify regions of long-range linkage disequilibrium, we further investigated signatures of past selective sweeps and how they reflect previous viral epidemics. Using independently-curated lists of human host proteins which interact physically or functionally with viruses (virus-interacting proteins; VIPs), we found enrichment in CKB for regions of long-range linkage disequilibrium at genes encoding VIPs for coronaviruses, but not DNA viruses. By contrast, we found no clear evidence for any VIP enrichment in UKB. These findings were supported by additional analyses using saltiLASSI, a selection-scan method robust to false positives caused by demographic events. By contrast, for GWAS signals for SARS-CoV-2 susceptibility (critical illness, hospitalization, and reported infection), there was no difference between UKB and CKB in the number located at or near signals of selection, as expected for a novel virus which has had no opportunity to impact the CKB/UKB study populations.

Together, these results provide evidence of selection events consistent with historical coronavirus epidemic(s) originating in East Asia. These results show how biobank-scale datasets and evolutionary genomics theory can provide insight into the study of past epidemics. The results also highlight how historic infectious disease epidemics can shape the genetic architecture of present-day human populations.

The online version contains supplementary material available at 10.1186/s12864-025-11876-4.