Department of Developmental Biology, Stanford University Medical School, Stanford, CA.
Kaiser Permanente Northern California, Division of Research, Oakland, CA.
Med Sci Sports Exerc. 2021 Aug 1;53(8):1748-1755. doi: 10.1249/MSS.0000000000002622.
This study aimed to screen the entire genome for genetic markers associated with risk for Achilles tendon injury.
A genome-wide association analysis was performed using data from the Kaiser Permanente Research Board and the UK Biobank. Achilles tendon injury cases were identified based on electronic health records from the Kaiser Permanente Research Board databank and the UK Biobank from individuals of European ancestry. Genome-wide association analyses from both cohorts were tested for Achilles tendon injury using a logistic regression model adjusting for sex, height, weight, and race/ethnicity using allele counts for single nucleotide polymorphisms (SNP). Previously identified genes within the literature were also tested for association with Achilles tendon injury.
There were a total of 12,354 cases of Achilles tendon injury and 483,080 controls within the two combined cohorts, with 67 SNP in three chromosomal loci demonstrating a genome-wide significant association with Achilles tendon injury. The first locus contains a single SNP (rs183364169) near the CDCP1 and TMEM158 genes on chromosome 3. The second locus contains 65 SNP in three independently segregating sets near the MPP7 gene on chromosome 10. The last locus contains a single SNP (rs4454832) near the SOX21 and GPR180 genes on chromosome 13. The current data were used to test 14 candidate genes previously reported to show an association with Achilles tendon injury, but none showed a significant association (all P > 0.05).
Three loci were identified as potential risk factors for Achilles tendon injury and deserve further validation and investigation of molecular mechanisms.
本研究旨在筛选与跟腱损伤风险相关的全基因组遗传标记。
使用 Kaiser Permanente 研究委员会和英国生物银行的数据进行全基因组关联分析。根据 Kaiser Permanente 研究数据库和英国生物银行的电子健康记录，从欧洲血统的个体中确定跟腱损伤病例。使用单核苷酸多态性（SNP）的等位基因计数，通过逻辑回归模型调整性别、身高、体重和种族/民族，对两个队列的全基因组关联分析进行跟腱损伤测试。还测试了文献中先前确定的基因与跟腱损伤的关联。
在两个合并队列中，共有 12354 例跟腱损伤病例和 483080 例对照，三个染色体位点的 67 个 SNP 与跟腱损伤具有全基因组显著关联。第一个位点包含位于染色体 3 上 CDCP1 和 TMEM158 基因附近的单个 SNP（rs183364169）。第二个位点包含位于染色体 10 上 MPP7 基因附近的三个独立分离集的 65 个 SNP。最后一个位点包含位于染色体 13 上 SOX21 和 GPR180 基因附近的单个 SNP（rs4454832）。目前的数据用于测试先前报道与跟腱损伤相关的 14 个候选基因，但均未显示出显著关联（所有 P > 0.05）。
确定了三个与跟腱损伤相关的潜在风险因素，值得进一步验证和研究分子机制。
