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IgA Nephropathy Genetic Risk Score to Estimate the Prevalence of IgA Nephropathy in UK Biobank

Sukcharoen, K; Sharp, SA; Thomas, NJ; Kimmitt, RA; Harrison, J; Bingham, C; Mozere, M; ... Oram, RA; + view all (2020) IgA Nephropathy Genetic Risk Score to Estimate the Prevalence of IgA Nephropathy in UK Biobank. Kidney International Reports , 5 (10) pp. 1643-1650. 10.1016/j.ekir.2020.07.012. Green open access

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Abstract

Background: IgA nephropathy (IgAN) is the commonest glomerulonephritis worldwide. Its prevalence is difficult to estimate, as people with mild disease do not commonly receive a biopsy diagnosis. We aimed to generate an IgA nephropathy genetic risk score (IgAN-GRS) and estimate the proportion of people with hematuria who had IgAN in the UK Biobank (UKBB). Methods: We calculated an IgAN-GRS using 14 single-nucleotide polymorphisms (SNPs) drawn from the largest European Genome-Wide Association Study (GWAS) and validated the IgAN-GRS in 464 biopsy-proven IgAN European cases from the UK Glomerulonephritis DNA Bank (UKGDB) and in 379,767 Europeans in the UKBB. We used the mean of IgAN-GRS to calculate the proportion of potential IgAN in 14,181 with hematuria and other nonspecific renal phenotypes from 379,767 Europeans in the UKBB. Results: The IgAN-GRS was higher in the IgAN cohort (4.30; 95% confidence interval [95% CI: 4.23–4.38) than in controls (3.98; 3.97–3.98; P < 0.0001). The mean GRS in UKBB participants with hematuria (n = 12,858) was higher (4.04; 4.02–4.06) than UKBB controls (3.98; 3.97–3.98; P < 0.0001) and higher in those with hematuria, hypertension, and microalbuminuria (n = 1323) (4.07; 4.02–4.13) versus (3.98; 3.97–3.98; P = 0.0003). Using the difference in these means, we estimated that IgAN accounted for 19% of noncancer hematuria and 28% with hematuria, hypertension, and microalbuminuria in UKBB. Conclusions: We used an IgAN-GRS to estimate the prevalence of IgAN contributing to common phenotypes that are not always biopsied. The noninvasive use of polygenic risk in this setting may have further utility to identify likely etiology of nonspecific renal phenotypes in large population cohorts.

Type: Article
Title: IgA Nephropathy Genetic Risk Score to Estimate the Prevalence of IgA Nephropathy in UK Biobank
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ekir.2020.07.012
Publisher version: https://doi.org/10.1016/j.ekir.2020.07.012
Language: English
Additional information: Published by Elsevier Inc. on behalf of the International Society of Nephrology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: Chronic kidney disease, epidemiology, Genetic Risk Scores, hematuria, IgA nephropathy
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10112192
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