
==== Front
medRxiv
MEDRXIV
medRxiv
Cold Spring Harbor Laboratory

10.1101/2024.09.13.24313664
preprint
1
Article
A GWAS of ACE Inhibitor-Induced Angioedema in a South African Population
Mugo Jacquiline W. http://orcid.org/0000-0003-0008-4358

Day Cascia
Choudhury Ananyo
Deetlefs Maria
Freercks Robert
Geraty Sian
Panieri Angelica
Cotchbos Christian
Ribeiro Melissa
Engelbrecht Adelein
Micklesfield Lisa K. http://orcid.org/0000-0002-4994-0779

Ramsay Michèle http://orcid.org/0000-0002-4156-4801

Pedretti Sarah
Peter Jonny http://orcid.org/0000-0002-2658-0723

15 9 2024
2024.09.13.24313664https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://medrxiv.org/lookup/doi/10.1101/2024.09.13.24313664
nihpp-2024.09.13.24313664.pdf
Abstract

Background

Angiotensin-converting enzyme inhibitor-induced angioedema (AE-ACEI) is a life-threatening adverse event and, globally, the commonest cause of emergency presentations with angioedema. Several large genome-wide association studies (GWAS) have found genomic associations with AE-ACEI. However, despite African Americans having a 5-fold increased risk of AE-ACEI, there are no published GWAS from Africa. The aim of this study was to conduct a case-control GWAS of AE-ACEI in a South African population and perform a meta-analysis with an African American and European American population.

Methods

The GWAS included 202 South African adults with a history of AE-ACEI and 513 controls without angioedema following angiotensin-converting enzyme inhibitor (ACEI) treatment for at least 2 years. A meta-analysis was conducted with GWAS summary statistics from an African American and European American cohort (from Vanderbilt/Marshfield with 174 cases and 489 controls).

Results

No SNPs attained genome-wide significance. However, 26 SNPs in the post-imputation standard GWAS of the South African cohort and 37 SNPs in the meta-analysis were associated to AE-ACEI with suggestive threshold(p-value<5.0×10 −06 ). Some of these SNPs were found to be located close to the genes PRKCQ and RIMS1, previously linked with drug-induced angioedema, and also close to the CSMD1 gene linked to ACEI cough, providing replication at the gene level, but with novel lead SNPs.

Conclusions

Our results highlight the importance of African populations to detect novel variants in replication studies. Further increased sampling across the continent and matched functional work are needed to confirm the importance of genetic variation in understanding the biology of AE-ACEI.
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