Family history and heritability of rotator cuff tears

Prior studies suggest familial clustering of rotator cuff tears (RCT) but are limited by sample size or by approach, and no study has estimated narrow-sense heritability of RCT. We perform a comprehensive assessment of the familial heritability of RCT.

We used data from 3 studies: the cuffGen study, Vanderbilt Health Biorepository (BioVU), and UK Biobank (UKB). In cuffGen, imaging confirmed RCT cases and controls completed a baseline questionnaire inquiring about their family history of RCT. In BioVU and UKB, RCT status was identified using electronic health record data, while family relatedness was estimated empirically with genome-wide genetic array data. We then evaluated the association between family relatedness and RCT status in all 3 studies using multivariable-adjusted logistic regression models while adjusting for age, sex, race and ethnicity, and genetic principal components (when appropriate). Then using genetic data in BioVU and UKB, we estimated narrow-sense/single nucleotide polymorphism (SNP)-based heritability for RCT, using a linkage disequilibrium score regression approach.

In the cuffGen study, RCT cases were more likely to report any family history of RCT (adjusted odds ratio [AOR]: 1.82; 95% confidence interval [CI]: 1.23-2.70) than controls. The association was stronger in first-degree relatives (AOR: 1.59; 95% CI: 1.12-2.26) than in second-degree relatives. In BioVU and UKB, familial relatedness is also associated with increased odds of RCT (BioVU: AOR: 1.21; 95% CI: 1.13-1.30; UKB: AOR: 1.09; 95% CI: 1.04-1.15). However, the strongest associations were observed in third-degree relatives in BioVU (AOR: 1.56; 95% CI: 1.10-2.14) and second-degree relatives in UKB (AOR: 1.25; 95% CI: 1.12-1.39) rather than first-degree relatives. In SNP-based heritability analyses, we observed that less than 1% of heritability of RCT was explained by SNPs (0.2% in BioVU and 0.75% in UKB), suggesting minimal contribution of genetic factors in heritability of RCT.

Although RCT cluster within families, SNP-based heritability explains less than 1% contribution to heritability of symptomatic RCT. These data suggest that genetic factors alone may have a minimal impact on symptomatic RCT susceptibility, whereas non-genetic familial factors, such as environmental or health care-related factors, represent plausible alternative explanations that warrant further investigation.