Influence of common genetic variants on childhood kidney outcomes

Background:Kidney measures in early life are associated with kidney disease in later life. We hypothesized that these associations are partly explained by common genetic variants that lead to both smaller kidneys with lower kidney function in early childhood and kidney disease in adulthood.Methods:We examined in a population-based prospective cohort study among 4,119 children the associations of a weighted genetic risk score combining 20 previously identified common genetic variants related to adult eGFR creat with kidney outcomes in children aged 6.0 years (95% range 5.7-7.8). Childhood kidney outcomes included combined kidney volume, glomerular filtration rate (eGFR) based on creatinine levels, and microalbuminuria based on albumin and creatinine urine levels.Results:We observed that the genetic risk score based on variants related to impaired kidney function in adults was associated with a smaller combined kidney volume (P value 3.0 × 10 -3) and with a lower eGFR (P value 4.0 × 10 -4) in children. The genetic risk score was not associated with microalbuminuria.Conclusion:Common genetic variants related to impaired kidney function in adults already lead to subclinical changes in childhood kidney outcomes. The well-known associations of kidney measures in early life with kidney disease in later life may at least be partly explained by common genetic variants.

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