Genomic Disorders in CKD across the Lifespan.

BACKGROUND: Genomic disorders (GDs) are associated with many comorbid outcomes, including CKD. Identification of GDs has diagnostic utility.

METHODS: We examined the prevalence of GDs among participants in the Chronic Kidney Disease in Children (CKiD) cohort II ( n =248), Chronic Renal Insufficiency Cohort (CRIC) study ( n =3375), Columbia University CKD Biobank (CU-CKD; n =1986), and the Family Investigation of Nephropathy and Diabetes (FIND; n =1318) compared with 30,746 controls. We also performed a phenome-wide association analysis (PheWAS) of GDs in the electronic MEdical Records and GEnomics (eMERGE; n =11,146) cohort.

RESULTS: We found nine out of 248 (3.6%) CKiD II participants carried a GD, replicating prior findings in pediatric CKD. We also identified GDs in 72 out of 6679 (1.1%) adult patients with CKD in the CRIC, CU-CKD, and FIND cohorts, compared with 199 out of 30,746 (0.65%) GDs in controls (OR, 1.7; 95% CI, 1.3 to 2.2). Among adults with CKD, we found recurrent GDs at the 1q21.1, 16p11.2, 17q12, and 22q11.2 loci. The 17q12 GD (diagnostic of renal cyst and diabetes syndrome) was most frequent, present in 1:252 patients with CKD and diabetes. In the PheWAS, dialysis and neuropsychiatric phenotypes were the top associations with GDs. In CRIC participants, GDs were associated with lower serum magnesium, lower educational achievement, and higher mortality risk.

CONCLUSION: Undiagnosed GDs are detected both in children and adults with CKD. Identification of GDs in these patients can enable a precise genetic diagnosis, inform prognosis, and help stratify risk in clinical studies. GDs could also provide a molecular explanation for nephropathy and comorbidities, such as poorer neurocognition for a subset of patients.