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

Abstract:
Background
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.

Results
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.

Conclusions
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.
Publication status:
Published
Peer review status:
Peer reviewed

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Files:
Publisher copy:
10.1186/s12864-025-11876-4

Authors

More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Nuffield Department of Population Health
Sub department:
Clinical Trial Service Unit
Role:
Author
ORCID:
0000-0003-4067-1100
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Nuffield Department of Population Health
Sub department:
Clinical Trial Service Unit
Role:
Author
ORCID:
0000-0002-7360-3385
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Nuffield Department of Population Health
Sub department:
Clinical Trial Service Unit
Role:
Author
ORCID:
0000-0002-0807-0682


More from this funder
Funder identifier:
https://ror.org/029chgv08
Grant:
088158/Z/09/Z
104085/Z/14/Z
212946/Z/18/Z
202922/Z/16/Z
More from this funder
Funder identifier:
https://ror.org/054225q67
Grant:
29186
More from this funder
Funder identifier:
https://ror.org/03x94j517
Grant:
MC_U137686851
MC_UU_00017/1
MC_UU_12026/2
MC_PC_14135


Publisher:
BioMed Central
Journal:
BMC Genomics More from this journal
Volume:
26
Issue:
1
Article number:
943
Publication date:
2025-10-21
Acceptance date:
2025-07-03
DOI:
EISSN:
1471-2164


Language:
English
Keywords:
Pubs id:
2134019
Local pid:
pubs:2134019
Deposit date:
2025-07-04
ARK identifier:

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