This design involves twins discordant for specific environmental factors or exposures, and twins discordant for disease outcomes or measures of morbidity.
Select twin pairs who differ (the most) in exposure

  • including measured genes (if DZ)
  • epigenetic changes (especially if MZ)

Analytic approach

  • Analyse differences in outcome against differences in exposure
  • Within- and between-pair models (Carlin et al., 2005; Gurrin et al., 2006)
  • Conditional logistic regression


  • Matched for both measured and unmeasured factors
  • Potential for causal inference
  • Similar to matched cohort studies:
  • Advantageous for rare exposures
  • Might need to cast a wide net
  • Of 1,300 female twin pairs in our Health and Lifestyle Questionnaire:
    • The average difference in pack years of smoking was 0.5 years
    • The average difference in mental health score was 0.08


  • Representative?


Carlin, J. B., Gurrin, L. C., Sterne, J. A. C., Morley, R. & Dwyer, T. (2005). Regression Models For Twin Studies: A Critical Review. International Journal of Epidemiology, 34, 1089-1099

Hopper, J. L., & Seeman. (1994). The Bone Density Of Female Twins Discordant For Tobacco Use. The New England Journal of Medicine, 330(6), 387-92.

Goldberg, J., & Fischer, M. (2005). Co-twin Control Methods. Encyclopedia of Statistics in Behavioral Science.

Gurrin, L. C., Carlin, J. B., Sterne, J. A. C., Dite, G. S. and Hopper, J. L. (2006). Using Bivariate Models to Understand between- and within-Cluster Regression Coefficients, with Application to Twin Data. Biometrics, 62, 745–751.

Scurrah, K. J., Kavanagh, A. M., Bentley, R. J., Thornton, L. E. and Harrap, S.B. (2015). Socioeconomic position in young adulthood is associated with BMI in Australian families. Journal of Public Health, 38(2), e39-e46..

Twins Research Australia

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Twins Research Australia has received continuous funding from the National Health and Medical Research Council (NHMRC) since 1981, most recently through a Centre of Research Excellence Grant (2015-2022). TRA is administered by the University of Melbourne.

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