Adamson, Walt E, Noyes, Harry 
ORCID: 0000-0002-0656-200X, Johnson, Paul, Cooper, Anneli, Monckton, Darren G, Ogunsola, John, Beckett-Hill, Georgia, Sullivan, Michael, Mark, Patrick, Parekh, Rulan S et al (show 1 more authors)
(2024)
Phenome-wide analysis reveals epistatic associations between APOL1 variants and chronic kidney disease and multiple other disorders.
EBioMedicine, 101.
p. 105000.
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Phenome-wide analysis reveals epistatic associations between APOL1 variants and chronic kidney disease and multiple other disorders Enhanced Reader.pdf - Open Access published version Download (9MB) | Preview |
Abstract
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. 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. 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. 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. This study was funded by the Wellcome Trust (209511/Z/17/Z) and H3Africa (H3A/18/004).
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Humans, Genetic Predisposition to Disease, Apolipoproteins, Risk Factors, Genotype, Renal Insufficiency, Chronic, Genome-Wide Association Study, Apolipoprotein L1 |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 19 Feb 2024 08:44 |
| Last Modified: | 02 Apr 2024 09:31 |
| DOI: | 10.1016/j.ebiom.2024.105000 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3178754 |
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