ArticleJournal of orthopaedic research : official publication of the Orthopaedic Research Society2026
Investigating the Association of Genetic Markers, Previously Identified by Genome-Wide Association Studies, With ACL Rupture in Multiple Cohorts.
Article in Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Several direct-to-consumer genetic tests claim to predict susceptibility to anterior cruciate ligament (ACL) rupture. Although not independently replicated, polymorphisms identified in a genome-wide association study-rs144051132 (T > A), rs186727643 (C > T), and/or rs188099931 (A > G)-have been incorporated into commercial tests to estimate cruciate ligament injury risk. This study aimed to evaluate whether these polymorphisms are associated with ACL rupture across multiple populations. We genotyped 906 clinically diagnosed ACL rupture cases, including 498 non-contact mechanism of injury ruptures (ACL-NC), and 679 controls (CON) from four European ancestry cohorts and a South African mixed-ancestry cohort. No significant differences were observed in genotype distributions between cases and controls in either the European cohorts (rs144051132 CON: 99.3% TT, 0.7% TA; ACL: 99.0% TT, 1.0% TA; rs186727643 CON: 100.0% CC; ACL: 99.9% CC, 0.1% CT or rs188099931 CON: 99.8% AA, 0.2% AG; ACL: 99.4% AA, 0.6% AG) or the mixed-ancestry cohort (rs144051132 CON: 99.0% TT, 1.0% TA; ACL: 97.9% TT, 2.1% TA; rs186727643 CON: 97.1% CC, 2.9% CT; ACL: 94.8% CC, 5.2% CT or rs188099931 CON: 99.0% AA, 1.0% AG; ACL: 100.0% AA). These polymorphisms were not associated with ACL rupture in the studied populations. The study was adequately powered to detect the larger effects previously reported but underpowered to detect the smaller effect reported for rs188099931. These results, as well as the rarity of the minor alleles, do not support the clinical validity of these polymorphisms as markers of ACL rupture risk.
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