Familial aggregation of hypospadias: a cohort study

Tine H Schnack, Slobodan Zdravkovic, Charlotte Myrup, Tine Westergaard, Kaare Christensen, Jan Wohlfahrt, Mads Melbye

Research output: Contribution to journalJournal articleResearchpeer-review


Hypospadias is one of the most common birth defects. However, its etiology remains largely unknown. The authors investigated the contribution of genetic and environmental factors to familial aggregation of hypospadias. Using Danish health registers, they identified 5,380 boys diagnosed with hypospadias in a cohort of 1,201,790 boys born in 1973-2005. Using binomial log-linear regression, they estimated recurrence risk ratios of hypospadias for male twin pairs and first-, second-, and third-degree relatives of a hypospadias case, which were 50.8 (95% confidence interval [CI]: 34.2, 75.5), 11.6 (95% CI: 9.75, 13.7), 3.27 (95% CI: 2.47, 4.34), and 1.33 (95% CI: 0.94, 1.88), respectively. Recurrence risk ratios did not differ for family members of a hypospadias case related to the same degree. In addition, the authors found no difference in the recurrence risk ratio for maternal compared with paternal second- and third-degree relatives of a hypospadias case. In conclusion, hypospadias was found to have a strong familial component and also to aggregate within more-distant relatives. Importantly, hypospadias was equally transmitted through the paternal and maternal sides of a family, and recurrence risk ratios for brothers and sons of a hypospadias case were similar. These findings indicate that genetic rather than intrauterine environmental factors have a principal role in causing familial hypospadias.
Original languageEnglish
JournalAmerican Journal of Epidemiology
Issue number3
Pages (from-to)251-256
Number of pages5
Publication statusPublished - 1. Feb 2008


  • Cohort Studies
  • Family
  • Humans
  • Hypospadias
  • Inheritance Patterns
  • Male
  • Odds Ratio
  • Registries
  • Twins

Fingerprint Dive into the research topics of 'Familial aggregation of hypospadias: a cohort study'. Together they form a unique fingerprint.

  • Cite this

    Schnack, T. H., Zdravkovic, S., Myrup, C., Westergaard, T., Christensen, K., Wohlfahrt, J., & Melbye, M. (2008). Familial aggregation of hypospadias: a cohort study. American Journal of Epidemiology, 167(3), 251-256. https://doi.org/10.1093/aje/kwm317