Genetic Determinants of Chronic Kidney Disease (CKD) in India: A Comprehensive Genomewide Association Study (GWAS)...

Chronic kidney disease (CKD) poses a major health burden globally and affects nearly 17% of the Indian population. Despite established risk factors such as diabetes and hypertension, significant interindividual variability suggests a genetic contribution to CKD susceptibility. This study explores genetic variants predisposing to CKD in the Indian population using a genomewide association approach.

A total of 90 patients with CKD and 90 healthy controls were genotyped using the Illumina Infinium Global Screening Array (640,000 markers). After stringent quality control, 5.7 million genetic markers were retained for analysis. Single-nucleotide polymorphisms (SNPs) were assessed using logistic regression including age, sex, and ten principal components as covariates. Variants meeting standard genomewide significance thresholds (p ≤ 5 × 10^-8) were considered significant.

The study identified 87 SNP loci associated with CKD, of which two genes, MPP7 and MAD1L1, reached genomewide significance. Variants with extremely high odds ratios (e.g., MAD1L1 OR > 1000) were interpreted as possible methodological artifacts. SNPs in PDZK1IP1, ANO3, C3AR1, FTO, and CD70 demonstrated suggestive biomarker potential (OR < 10, p < 10^-4), warranting replication in larger cohorts. These findings provide new insights into genes involved in tubular integrity, immune activation, and metabolic regulation in CKD.

This genomewide analysis represents one of the first studies on CKD genetics in the Indian population. While the MPP7 variant emerges as a credible susceptibility locus, several other SNPs show promising biomarker potential. Larger, multiethnic studies and functional validation are needed to confirm their roles in CKD pathogenesis and therapeutic targeting.