Familial Risk and Its Interaction With Body Mass Index and Physical Activity in Anterior Cruciate Ligament Injury Among First-Degree Relatives: A Population-Based Cohort Study

Am J Sports Med. 2021 Oct;49(12):3312-3321. doi: 10.1177/03635465211032643. Epub 2021 Sep 7.


Background: Genetic and behavioral risk factors have been suggested to play a role in anterior cruciate ligament (ACL) injury. However, population-based familial risk estimates are unavailable.

Purpose: To quantify familial risk of ACL injury among first-degree relatives (FDRs) after controlling for certain behavioral risk factors. To estimate the combined effect of family history and body mass index (BMI) or physical activity on the risk of ACL injury.

Study design: Cohort study; Level of evidence, 3.

Methods: Using nationwide data from the Korean National Health Insurance and National Health Screening Program databases on kinship, lifestyle habits, and anthropometrics, 5,184,603 individuals with blood-related FDRs were identified from 2002 to 2018. Familial risk of ACL injury, as represented as incidence risk ratios (IRRs) with 95% CIs, was analyzed using Cox proportional hazards models among individuals with versus without affected FDRs. Analyses were adjusted for age, sex, and behavioral risk factors. Interaction testing between familial history and BMI or physical activity was performed on an additive scale.

Results: The risk of ACL injury was 1.79-fold higher (IRR, 1.79; 95% CI, 1.73-1.85) among individuals with versus without affected FDRs, and the incidence was 12.61 per 10,000 person-years. The IRR (95% CI) was highest with affected twins at 4.49 (3.01-6.69), followed by siblings at 2.31 (2.19-2.44), the father at 1.58 (1.49-1.68), and the mother at 1.52 (1.44-1.61). High BMI and high level of physical activity were significantly associated with the risk of ACL injury. Individuals with positive family history and either high BMI or physical activity had a 2.59- and 2.45-fold increased risk of injury as compared with the general population, respectively, and the combined risks exceeded the sum of their independent risks.

Conclusion: Familial factors are risk factors for ACL injury with an additional contribution of 2 behavioral factors: BMI and physical activity level. A significant interaction was observed between family history of ACL injury and high BMI/level of physical activity.

Keywords: additive scale; behavioral risk factors; familial risk; incidence; interaction.

MeSH terms

  • Anterior Cruciate Ligament Injuries* / epidemiology
  • Anterior Cruciate Ligament Injuries* / surgery
  • Anterior Cruciate Ligament Reconstruction*
  • Body Mass Index
  • Cohort Studies
  • Exercise
  • Genetic Predisposition to Disease
  • Humans
  • Risk Factors