Prioritizing autoimmunity risk variants for functional analyses by fine-mapping mutations under natural selection

Vasili Pankratov, Milyausha Yunusbaeva, Sergei Ryakhovsky, Maksym Zarodniuk and Bayazit Yunusbayev ()
Additional contact information
Vasili Pankratov: University of Tartu, Institute of Genomics, Centre for Genomics, Evolution and Medicine
Milyausha Yunusbaeva: ITMO University, SCAMT Institute
Sergei Ryakhovsky: ITMO University, SCAMT Institute
Maksym Zarodniuk: University of Tartu, Institute of Bio- and Translational Medicine
Bayazit Yunusbayev: University of Tartu, Institute of Genomics, Centre for Genomics, Evolution and Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract Pathogen-driven selection shaped adaptive mutations in immunity genes, including those contributing to inflammatory disorders. Functional characterization of such adaptive variants can shed light on disease biology and past adaptations. This popular idea, however, was difficult to test due to challenges in pinpointing adaptive mutations in selection footprints. In this study, using a local-tree-based approach, we show that 28% of risk loci (153/535) in 21 inflammatory disorders bear footprints of moderate and weak selection, and part of them are population specific. Weak selection footprints allow partial fine-mapping, and we show that in 19% (29/153) of the risk loci under selection, candidate disease variants are hitchhikers, and only in 39% of cases they are likely selection targets. We predict function for a subset of these selected SNPs and highlight examples of antagonistic pleiotropy. We conclude by offering disease variants under selection that can be tested functionally using infectious agents and other stressors to decipher the poorly understood link between environmental stressors and genetic risk in inflammatory conditions.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-34461-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34461-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-34461-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().