TY - JOUR
T1 - Association of polygenic scores with chronic kidney disease phenotypes in a longitudinal study of older adults
AU - Bakshi, Andrew
AU - Jefferis, Julia
AU - Wolfe, Rory
AU - Wetmore, James B.
AU - McNeil, John J.
AU - Murray, Anne M.
AU - Polkinghorne, Kevan R.
AU - Mallett, Andrew J.
AU - Lacaze, Paul
N1 - Funding Information:
AMM, KRP, and RW have received grants from the National Institutes of Health for the ASPREE trial and cohort. JBW has received grants from the National Institutes of Health, Merck, Glaco Smith Line, and Pfizer and meeting travel support and honoraria for educational events from Vifor, all outside of this work. AJM has received grants from the Medical Research Future Fund, Australian Government Department of Health, Townsville Hospital, and Health Services and meeting travel support from Otsuka, all outside of this work. All the other authors declared no competing interests.
Funding Information:
This work was supported by an ASPREE Flagship cluster grant (including the Commonwealth Scientific and Industrial Research Organisation, Monash University, Menzies Research Institute, Australian National University, and University of Melbourne); by grants (U01AG029824 and U19AG062682) from the National Institute on Aging and the National Cancer Institute at the National Institutes of Health and from the National Health and Medical Research Council of Australia ( 334047 and 1127060 ); and by Monash University and the Victorian Cancer Agency. Genotyping of the ASPREE cohort was funded by Bioplatforms Australia (National Framework Initiative). AJM is supported by a Queensland Health Advancing Clinical Research Fellowship. PL is supported by a National Heart Foundation Future Leader Fellowship.
Publisher Copyright:
© 2023 International Society of Nephrology
PY - 2023/6
Y1 - 2023/6
N2 - 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.
AB - 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.
KW - chronic kidney disease
KW - geriatric nephrology
KW - polygenic risk score
UR - http://www.scopus.com/inward/record.url?scp=85153211006&partnerID=8YFLogxK
U2 - 10.1016/j.kint.2023.03.017
DO - 10.1016/j.kint.2023.03.017
M3 - Article
C2 - 37001602
AN - SCOPUS:85153211006
SN - 0085-2538
VL - 103
SP - 1156
EP - 1166
JO - Kidney International
JF - Kidney International
IS - 6
ER -