Adamson, W. E. et al. (2024) Phenome-wide analysis reveals epistatic associations between APOL1 variants and chronic kidney disease and multiple other disorders. EBioMedicine, 101, 105000. (doi: 10.1016/j.ebiom.2024.105000) (PMID:38360481) (PMCID:PMC10944146)
![[img]](https://eprints.gla.ac.uk/style/images/fileicons/text.png) |
Text
317260Suppl.pdf - Supplemental Material 579kB |
|
Text
317260.pdf - Published Version Available under License Creative Commons Attribution. 777kB |
Abstract
Background: APOL1 variants G1 and G2 are common in populations with recent African ancestry. They are associated with protection from African sleeping sickness, however homozygosity or compound heterozygosity for these variants is associated with chronic kidney disease (CKD) and related conditions. What is not clear is the extent of associations with non-kidney-related disorders, and whether there are clusters of diseases associated with individual APOL1 genotypes. Methods: Using a cohort of 7462 UK Biobank participants with recent African ancestry, we conducted a phenome-wide association study investigating associations between individual APOL1 genotypes and conditions identified by the International Classification of Disease phenotypes. Findings: We identified 27 potential associations between individual APOL1 genotypes and a diverse range of conditions. G1/G2 compound heterozygotes were specifically associated with 26 of these conditions (all deleteriously), with an over-representation of infectious diseases (including hospitalisation and death resulting from COVID-19). The analysis also exposed complexities in the relationship between APOL1 and CKD that are not evident when risk variants are grouped together: G1 homozygosity, G2 homozygosity, and G1/G2 compound heterozygosity were each shown to be associated with distinct CKD phenotypes. The multi-locus nature of the G1/G2 genotype means that its associations would go undetected in a standard genome-wide association study. Interpretation: Our findings have implications for understanding health risks and better-targeted detection, intervention, and therapeutic strategies, particularly in populations where APOL1 G1 and G2 are common such as in sub-Saharan Africa and its diaspora. Funding: This study was funded by the Wellcome Trust (209511/Z/17/Z) and H3Africa (H3A/18/004).
| Item Type: | Articles |
|---|---|
| Additional Information: | This study was funded by the Wellcome Trust (209511/Z/17/Z) and H3Africa (H3A/18/004). |
| Keywords: | APOL1, phenome, chronic kidney disease, UK Biobank, COVID-19. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Beckett-Hill, Miss Georgia and Johnson, Dr Paul and MacLeod, Professor Annette and Mark, Professor Patrick and Sullivan, Dr Michael and Monckton, Professor Darren and Ogunsola, Mr John and Cooper, Dr Anneli and Adamson, Dr Walt |
| Creator Roles: | Adamson, W.Conceptualization, Formal analysis, Writing – original draft Johnson, P.Methodology, Supervision, Writing – review and editing Cooper, A.Writing – review and editing Monckton, D.Methodology, Writing – review and editing Ogunsola, J.Writing – review and editing Beckett-Hill, G.Methodology, Writing – original draft Sullivan, M.Methodology, Supervision Mark, P.Methodology, Supervision, Writing – review and editing MacLeod, A.Methodology, Resources, Supervision, Writing – original draft, Writing – review and editing |
| Authors: | Adamson, W. E., Noyes, H., Johnson, P., Cooper, A., Monckton, D. G., Ogunsola, J., Beckett-Hill, G., Sullivan, M., Mark, P., Parekh, R. S., and MacLeod, A. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health College of Medical Veterinary and Life Sciences > School of Molecular Biosciences |
| Journal Name: | EBioMedicine |
| Publisher: | Elsevier |
| ISSN: | 2352-3964 |
| ISSN (Online): | 2352-3964 |
| Published Online: | 14 February 2024 |
| Copyright Holders: | Copyright © 2024 The Authors |
| First Published: | First published in EBioMedicine 101:105000 |
| Publisher Policy: | Reproduced under a Creative Commons License |
University Staff: Request a correction | Enlighten Editors: Update this record
Funder and Project Information
Funder and Project Information