Limited clinical utility for GWAS or polygenic risk score for postoperative acute kidney injury in non-cardiac surgery in European-ancestry patients

• Published in: BMC nephrology 2022-10, Vol.23 (1), p.339-339, Article 339
• Main Authors: Larach, Daniel B, Lewis, Adam, Bastarache, Lisa, Pandit, Anita, He, Jing, Sinha, Anik, Douville, Nicholas J, Heung, Michael, Mathis, Michael R, Mosley, Jonathan D, Wanderer, Jonathan P, Kheterpal, Sachin, Zawistowski, Matthew, Brummett, Chad M, Siew, Edward D, Robinson-Cohen, Cassianne, Kertai, Miklos D
• Format: Article
• Language: English
• Subjects: Acute kidney injury; Acute Kidney Injury - diagnosis; Acute Kidney Injury - epidemiology; Acute Kidney Injury - genetics; Acute renal failure; Adult; Age; Anesthesia; Body mass index; Clinical medicine; Codes; Comorbidity; Complications; Creatinine; Evaluation; Female; Gender; Genetic aspects; Genetic diversity; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genomics; Glomerular Filtration Rate; Hemoglobin; Heritability; Humans; Kidney diseases; Kidneys; Male; Meta-analysis; Mortality; Multifactorial traits; Nephrology; Patients; Polygenic inheritance; Polygenic risk score; Population studies; Postoperative Complications - epidemiology; Postoperative Complications - genetics; Quality control; Retrospective Studies; Risk Factors; Risk groups; Surgery
• ISSN: 1471-2369; 1471-2369
• DOI: 10.1186/s12882-022-02964-8

Prior studies support a genetic basis for postoperative acute kidney injury (AKI). We conducted a genome-wide association study (GWAS), assessed the clinical utility of a polygenic risk score (PRS), and estimated the heritable component of AKI in patients who underwent noncardiac surgery. We performed a retrospective large-scale genome-wide association study followed by a meta-analysis of patients who underwent noncardiac surgery at the Vanderbilt University Medical Center ("Vanderbilt" cohort) or Michigan Medicine, the academic medical center of the University of Michigan ("Michigan" cohort). In the Vanderbilt cohort, the relationship between polygenic risk score for estimated glomerular filtration rate and postoperative AKI was also tested to explore the predictive power of aggregating multiple common genetic variants associated with AKI risk. Similarly, in the Vanderbilt cohort genome-wide complex trait analysis was used to estimate the heritable component of AKI due to common genetic variants. The study population included 8248 adults in the Vanderbilt cohort (mean [SD] 58.05 [15.23] years, 50.2% men) and 5998 adults in Michigan cohort (56.24 [14.76] years, 49% men). Incident postoperative AKI events occurred in 959 patients (11.6%) and in 277 patients (4.6%), respectively. No loci met genome-wide significance in the GWAS and meta-analysis. PRS for estimated glomerular filtration rate explained a very small percentage of variance in rates of postoperative AKI and was not significantly associated with AKI (odds ratio 1.050 per 1 SD increase in polygenic risk score [95% CI, 0.971-1.134]). The estimated heritability among common variants for AKI was 4.5% (SE = 4.5%) suggesting low heritability. The findings of this study indicate that common genetic variation minimally contributes to postoperative AKI after noncardiac surgery, and likely has little clinical utility for identifying high-risk patients.