Understanding statistical principles in correlation, causation and moderation in human disease

Michael P Jones, Marjorie M Walker and John R Attia
Med J Aust 2017; 207 (3): . || doi: 10.5694/mja16.00697
Published online: 7 August 2017

We are all familiar with the expression “correlation does not imply causation”, but often causation is exactly what we need to determine. For example, one may want to understand whether the use of MP3 players with earbuds causes partial hearing loss, whether holding mobile telephones to the ear causes brain cancer or whether parents’ exposure to toxic chemicals during conception or pregnancy causes birth defects in children. Non-causal risk factors can be useful, but eventually, what we really want to understand is causation. Because the causal connection between exposure to risk factor and disease outcome is often complex or poorly understood, what researchers can truly study is whether an association exists or not. This article explains how we can move from correlation and association to causal interpretation of data, and what statistical evidence is needed to support causal conclusions.

  • 1 Macquarie University, Sydney, NSW
  • 2 University of Newcastle, Newcastle, NSW
  • 3 Centre for Clinical Epidemiology and Biostatistics, University of Newcastle, Newcastle, NSW
  • 4 John Hunter Hospital, Newcastle, NSW


Competing interests:

No relevant disclosures.

  • 1. Walker MM, Talley NJ, Prabhakar M, et al. Duodenal mastocytosis, eosinophilia and intraepithelial lymphocytosis as possible disease markers in the irritable bowel syndrome and functional dyspepsia. Aliment Pharmacol Ther 2009; 29: 765-773.
  • 2. Goldacre B. Is the conflict of interest unacceptable when drug companies conduct trials on their own drugs? Yes. BMJ 2009; 339.
  • 3. Mukai K, Tsai M, Starkl P, et al. IgE and mast cells in host defense against parasites and venoms. Semin Immunopathol 2016; 38: 581-603.
  • 4. Doll R, Hill AB. Smoking and carcinoma of the lung. Br Med J 1950; 2: 739-748.
  • 5. Stolley PD. When genius errs: RA Fisher and the lung cancer controversy. Am J Epidemiol 1991; 133: 416-425.
  • 6. Longstreth GF, Thompson WG, Chey WD, et al. Functional bowel disorders. Gastroenterology 2006; 130: 1480-1491.
  • 7. Koloski NA, Jones M, Kalantar J, et al. The brain–gut pathway in functional gastrointestinal disorders is bidirectional: a 12-year prospective population-based study. Gut 2012; 61: 1284-1290.
  • 8. Liebregts T, Adam B, Bredack C, et al. Immune activation in patients with irritable bowel syndrome. Gastroenterology 2007; 132: 913-920.
  • 9. Hill AB. The environment and disease: association or causation? Proc R Soc Med 1965; 58: 295-300.
  • 10. Maxwell SE, Cole DA. Bias in cross-sectional analyses of longitudinal mediation. Psychol Methods 2007; 12: 23-44.
  • 11. Kershaw KN, Mezuk B, Abdou CM, et al. Socioeconomic position, health behaviors, and C-reactive protein: a moderated-mediation analysis. Health Psychol 2010; 29: 307-316.


remove_circle_outline Delete Author
add_circle_outline Add Author

Do you have any competing interests to declare? *

I/we agree to assign copyright to the Medical Journal of Australia and agree to the Conditions of publication *
I/we agree to the Terms of use of the Medical Journal of Australia *
Email me when people comment on this article

Online responses are no longer available. Please refer to our instructions for authors page for more information.