Koizia Louis John, Giovannantonio Matteo Di, Zhang Ping, Fertleman Michael Barry, Lole Harris Benjamin Howell
Cutrale Perioperative and Ageing Research Group, Imperial College London, London, UK.
Department of Oncology, University of Oxford, Oxford, UK.
Geriatr Orthop Surg Rehabil. 2025 Apr 16;16:21514593251336568. doi: 10.1177/21514593251336568. eCollection 2025.
Hip fractures are among the most common major orthopaedic injuries globally, with one in three women and one in twelve men projected to sustain a hip fracture in their lifetime. Identifying genetic factors that contribute to hip fracture risk could improve risk stratification and inform prevention strategies. This study aims to identify genetic variants associated with hip fracture susceptibility through a genome-wide association study (GWAS).
A GWAS was undertaken using the UK Biobank to identify risk loci for hip fractures.
At the time of analysis, 2165 neck of femur fractures were identified among the 502 507 participants. Thirteen SNPs in five putative haplotypes were identified as significantly associated with hip fracture using the stringent GWAS threshold of 5E-8. Two of these loci appear to affect HOXC8, either by influencing the 3' UTR (rs4142680[T]) or via the miRNA hsa-miR-196a (rs11614913[T]). These two SNPs were also found to be expression quantitative trait loci for homeobox-C cluster genes (HOXC6, HOXC9, and HOXC-AS1).
Polymorphisms affecting homeobox-C cluster genes influence hip fracture risk in the general population. Future research should focus on validating these genetic associations and exploring optimal therapeutic interventions that could mitigate fracture risk in subpopulations carrying these polymorphisms.
髋部骨折是全球最常见的主要骨科损伤之一，预计每三名女性和每十二名男性中就有一人一生中会发生髋部骨折。识别导致髋部骨折风险的遗传因素有助于改善风险分层并为预防策略提供依据。本研究旨在通过全基因组关联研究（GWAS）识别与髋部骨折易感性相关的基因变异。
利用英国生物银行进行全基因组关联研究，以确定髋部骨折的风险位点。
在分析时，502507名参与者中确定了2165例股骨颈骨折。使用5E-8的严格全基因组关联研究阈值，在五个假定单倍型中鉴定出13个单核苷酸多态性（SNP）与髋部骨折显著相关。其中两个位点似乎通过影响3'非翻译区（rs4142680[T]）或通过miRNA hsa-miR-196a（rs11614913[T]）影响HOXC8。还发现这两个SNP是同源盒C簇基因（HOXC6、HOXC9和HOXC-AS1）的表达数量性状位点。
影响同源盒C簇基因的多态性影响普通人群的髋部骨折风险。未来的研究应集中于验证这些遗传关联，并探索能够降低携带这些多态性的亚人群骨折风险的最佳治疗干预措施。
