Abstract
Introduction: In this study, we evaluated the genetic predisposition to AKI using genome-wide association study (GWAS) in patients undergoing elective off-pump-CABG (OP-CABG). Methods: Patients of South Asian ancestry were categorized into four cohorts as follows: (A) patients with normal renal function undergoing OP-CABG (eGFR>60ml/min/m2) (n=754; AKI - 81, Non-AKI-673); (B) patients with renal dysfunction (eGFR<60ml/min/m2; not needing dialysis) undergoing OP-CABG (n=263; AKI-169, non-AKI-89); (C) patients with renal dysfunction with no symptomatic/known heart disease (n=92); (D) age-matched healthy control population (with normal kidney function, without symptomatic/known heart disease) (n=826). Renal function was considered to be normal, if the serum creatinine was less than 1.3mg% and/or estimated glomerular filtration rate was greater than 60ml/min/1.7 m 2 . Genotyping was performed using Infinium Global Screening Array-24 v3.0 BeadChip from Illumina, which included 6,54,027 markers. GWAS analysis was performed using age, genders and top10 principal components as covariates using logistic regression using PLINK 2.0. Postoperative AKI was defined based on Kidney Disease Improving Global Outcomes guidelines. Results: There were 754 participants with good renal function undergoing OP-CABG; among them, 81 subjects developed AKI postoperatively. The GWAS analysis revealed 607 markers with a suggestive significance p-value threshold of 1e-4. A modest signal was observed on chromosome 11 region, covering genes such as COX8A, NAA40, RCOR. The gene-based test in FUMA annotation revealed genes, MARCOD2, CNTN4, MAGI2 etc. as top hits. However, none of the markers remained significant after multiple testing corrections using Bonferroni and Benjamini-Hochberg. Conclusions: The GWAS revealed an association signal on chromosome 11, which is suggestive and needs to be pursued further in a larger sample set.
Published Version
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