title: Genome-wide association screens for Achilles tendon and ACL tears and tendinopathy.
abstract: Achilles tendinopathy or rupture and anterior cruciate ligament (ACL) rupture are substantial injuries affecting athletes, associated with delayed recovery or inability to return to competition. To identify genetic markers that might be used to predict risk for these injuries, we performed genome-wide association screens for these injuries using data from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort consisting of 102,979 individuals. We did not find any single nucleotide polymorphisms (SNPs) associated with either of these injuries with a p-value that was genome-wide significant (p<5x10-8). We found, however, four and three polymorphisms with p-values that were borderline significant (p<10-6) for Achilles tendon injury and ACL rupture, respectively. We then tested SNPs previously reported to be associated with either Achilles tendon injury or ACL rupture. None showed an association in our cohort with a false discovery rate of less than 5%. We obtained, however, moderate to weak evidence for replication in one case; specifically, rs4919510 in MIR608 had a p-value of 5.1x10-3 for association with Achilles tendon injury, corresponding to a 7% chance of false replication. Finally, we tested 2855 SNPs in 90 candidate genes for musculoskeletal injury, but did not find any that showed a significant association below a false discovery rate of 5%. We provide data containing summary statistics for the entire genome, which will be useful for future genetic studies on these injuries.
authors.affiliation: Department Developmental Biology, Stanford University Medical Center, Stanford CA, United States of America.
authors.forename: Stuart K
authors.identifier: http://orcid.org/0000-0001-8887-5095
authors.initials: SK
authors.lastname: Kim
authors.affiliation: Department Developmental Biology, Stanford University Medical Center, Stanford CA, United States of America.|Department Health Research and Policy, Division of Epidemiology, Stanford University Medical Center, Stanford CA, United States of America.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Roos
authors.affiliation: Department Developmental Biology, Stanford University Medical Center, Stanford CA, United States of America.|Department Health Research and Policy, Division of Epidemiology, Stanford University Medical Center, Stanford CA, United States of America.
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Roos
authors.affiliation: Department Orthopaedic Surgery, Stanford University Medical Center, Stanford CA, United States of America.
authors.forename: John P
authors.initials: JP
authors.lastname: Kleimeyer
authors.affiliation: Department Orthopaedic Surgery, Stanford University Medical Center, Stanford CA, United States of America.
authors.forename: Marwa A
authors.initials: MA
authors.lastname: Ahmed
authors.affiliation: College of Medicine, California Northstate University, Elk Grove CA, United States of America.
authors.forename: Gabrielle T
authors.initials: GT
authors.lastname: Goodlin
authors.affiliation: Department Orthopaedic Surgery, Stanford University Medical Center, Stanford CA, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Fredericson
authors.affiliation: Department of Medicine, Stanford Prevention Research Center, Stanford University School of Medicine, Stanford CA, United States of America.|Department of Health Research and Policy, Division of Epidemiology, Stanford University School of Medicine, Stanford CA, United States of America.|Department of Statistics, Stanford University School of Humanities and Sciences, Stanford CA, United States of America.
authors.forename: John P A
authors.initials: JP
authors.lastname: Ioannidis
authors.affiliation: Kaiser Permanente Northern California, Division of Research, Oakland, California, United States of America.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Avins
authors.affiliation: Department Orthopaedic Surgery, Stanford University Medical Center, Stanford CA, United States of America.
authors.forename: Jason L
authors.initials: JL
authors.lastname: Dragoo
mesh_terms: D000125:Achilles Tendon / Q000000981:diagnostic imaging / Q000293:injuries / Q000503:physiopathology; D000368:Aged; D016118:Anterior Cruciate Ligament / Q000000981:diagnostic imaging / Q000503:physiopathology; D000070598:Anterior Cruciate Ligament Injuries / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D052256:Tendinopathy / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology
chemical_list: C000591804:MIRN608 microRNA, human; D035683:MicroRNAs