A twin study of genetic influences on nephrolithiasis in women and men

Background: Nephrolithiasis is a complex phenotype influenced by both genetic and environmental factors. Previously we found a genetic component to stone disease using a sample of male twin pairs. We now report on the genetic contribution to stones in a sample of female and male twin pairs.

Methods: We conducted a classic twin study of kidney stones using the Washington State Twin Registry. Data were collected by questionnaire to obtain self-reported history of kidney stones. Univariate structural equation modeling was used to determine the relative contributions of additive genetics, common environment, and unique environment.

Results: There were 7053 same-sex pairs with kidney stone data. The mean age of the sample was 39 years, similar in women and men. The prevalence of stones was 4.9% of women and 6.2% of men. We found significant contributions from genetics and the unique environment (P < 0.05 for both) for the risk for stone disease in women and men. There was no significant contribution of the common environment for either sex. After adjusting for age, heritability was 46% (95% confidence interval 0.36-0.56) in women and 57% (0.46-0.68) in men, which was significantly different (P < 0.05).

Conclusions: Nephrolithiasis in women has a heritable component less than that we again demonstrate in men. This finding may in part explain why more stone formers are men than women. Women twins demonstrated a greater effect of the unique environment on stone prevalence. The specific environmental risk factors that account for this effect are not currently known.

Goldfarb DS, Avery AR, Beara-Lasic L, Duncan GE, Goldberg J. A Twin Study of Genetic Influences on Nephrolithiasis in Women and Men. Kidney Int Rep. 2018 Nov 29;4(4):535-540. PMC6451147.