Association of polygenic scores with chronic kidney disease phenotypes in a longitudinal study of older adults

Bakshi, Andrew, Jefferis, Julia, Wolfe, Rory, Wetmore, James B., McNeil, John J., Murray, Anne M., Polkinghorne, Kevan R., Mallett, Andrew J., and Lacaze, Paul (2023) Association of polygenic scores with chronic kidney disease phenotypes in a longitudinal study of older adults. Kidney International, 103 (6). pp. 1156-1166.

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Abstract

Risk of chronic kidney disease (CKD) is influenced by environmental and genetic factors and increases sharply in individuals 70 years and older. Polygenic scores (PGS) for kidney disease-related traits have shown promise but require validation in well-characterized cohorts. Here, we assessed the performance of recently developed PGSs for CKD-related traits in a longitudinal cohort of healthy older individuals enrolled in the Australian ASPREE randomized controlled trial of daily low-dose aspirin with CKD risk at baseline and longitudinally. Among 11,813 genotyped participants aged 70 years or more with baseline eGFR measures, we tested associations between PGSs and measured eGFR at baseline, clinical phenotype of CKD, and longitudinal rate of eGFR decline spanning up to six years of follow-up per participant. A PGS for eGFR was associated with baseline eGFR, with a significant decrease of 3.9 mL/min/1.73m2 (95% confidence interval -4.17 to -3.68) per standard deviation (SD) increase of the PGS. This PGS, as well as a PGS for CKD stage 3 were both associated with higher risk of baseline CKD stage 3 in cross-sectional analysis (Odds Ratio 1.75 per SD, 95% confidence interval 1.66-1.85, and Odds Ratio 1.51 per SD, 95% confidence interval 1.43-1.59, respectively). Longitudinally, two separate PGSs for eGFR slope were associated with significant kidney function decline during follow-up. Thus, our study demonstrates that kidney function has a considerable genetic component in older adults, and that new PGSs for kidney disease-related phenotypes may have potential utility for CKD risk prediction in advanced age.

Item ID: 79064
Item Type: Article (Research - C1)
ISSN: 1523-1755
Keywords: chronic kidney disease, geriatric nephrology, polygenic risk score
Copyright Information: © 2023, International Society of Nephrology. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Funders: National Health and Medical Research Council (NHMRC)
Projects and Grants: NHMRC 334047, NHMRC 1127060
Date Deposited: 08 Nov 2023 22:47
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320214 Nephrology and urology @ 100%
SEO Codes: 20 HEALTH > 2001 Clinical health > 200101 Diagnosis of human diseases and conditions @ 100%
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