Nature versus nurture in gout: a twin study

Am J Med. 2012 May;125(5):499-504. doi: 10.1016/j.amjmed.2011.11.010. Epub 2012 Feb 22.


Background: Gouty arthritis (gout) is the most common inflammatory arthritis in the United States and several other countries. Some rare forms of gout have a known genetic basis, but the relative importance of genetic factors on the risk for the lifetime prevalence of gout is not clear.

Methods: We performed a heritability analysis for hyperuricemia and gout among 514 unselected, all-male twin pairs who were a part of the National Heart, Lung, and Blood Institute twin study, a prospective observational cohort study. Statistical analyses were performed using structural equation models and maximum likelihood methods. The covariates used for adjustment in the structural equation models were identified using bivariate logistic regressions.

Results: The study population included 253 monozygotic (MZ) and 261 dizygotic (DZ) twin pairs, aged 48 (±3) years at baseline and followed for a mean of 34 years. The lifetime prevalence of gout did not differ between MZ and DZ twins. The concordance of hyperuricemia was 53% in MZ and 24% in DZ twin pairs (P<.001). Models that quantified the relative contribution of genetic and environmental factors on phenotypic variance showed that individual variability in gout was substantially influenced by environmental factors shared between co-twins and not by genetic factors. In contrast, individual differences in hyperuricemia were influenced significantly by genetic factors.

Conclusion: Hyperuricemia is a genetic trait. Outside the context of rare genetic disorders, risk for gout is determined by the environment. This has implications for prevention and treatment approaches.

Trial registration: NCT00005124.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Diseases in Twins*
  • Genetic Predisposition to Disease*
  • Gout / etiology*
  • Gout / genetics*
  • Humans
  • Hyperuricemia / genetics
  • Male
  • Middle Aged

Associated data