Understanding the mechanisms of hip disease, such as osteoarthritis (OA), is crucial to advance their treatment. Such hip diseases often involve specific morphological changes. Genetic variations, called single nucleotide polymorphisms (SNPs), influence various hip morphological parameters. This study investigated the biological relevance of SNPs correlated to hip morphology in genome-wide association studies (GWAS). The SNP-associated genes were compared to genes associated with OA in other joints, aiming to see if the same genes play a role in both hip development and the risk of OA in other lower limb joints. A systematic literature review was conducted to identify SNPs correlated with hip morphology, based on the Population, Intervention, Comparison, Outcome, and Study (PICOS) framework. Afterwards, Gene Ontology (GO) analysis was performed, using EnrichR, on the SNP-associated genes and compared with non-hip OA-associated genes, across different databases. Reviewing 49 GWAS identified 436 SNPs associated with hip joint morphology, encompassing variance in bone size, structure and shape. Among the SNP-associated genes, plays a pivotal role in size, impacts bone structure, and affects shape. Overall, skeletal system development, regulation of cell differentiation, and chondrocyte differentiation emerged as crucial processes influencing hip morphology. Eighteen percent of GWAS-identified genes related to hip morphology were also associated with non-hip OA. Our findings indicate the existence of multiple shared genetic mechanisms across hip morphology and OA, highlighting the necessity for more extensive research in this area, as in contrast to the hip, the genetic background on knee or foot morphology remains largely understudied.

中文翻译：

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对髋关节形态和骨关节炎背后的单核苷酸多态性的系统回顾和跨数据库分析揭示了共同的机制


了解骨关节炎 (OA) 等髋关节疾病的机制对于推进治疗至关重要。此类髋部疾病通常涉及特定的形态变化。称为单核苷酸多态性 (SNP) 的遗传变异会影响各种髋关节形态参数。本研究调查了全基因组关联研究 (GWAS) 中与髋部形态相关的 SNP 的生物学相关性。将 SNP 相关基因与其他关节中与 OA 相关的基因进行比较，旨在了解相同的基因是否在髋关节发育和其他下肢关节中 OA 风险中发挥作用。基于人口、干预、比较、结果和研究 (PICOS) 框架，进行了系统的文献综述，以确定与髋关节形态相关的 SNP。随后，使用 EnrichR 对 SNP 相关基因进行基因本体 (GO) 分析，并在不同数据库中与非髋关节 OA 相关基因进行比较。回顾 49 个 GWAS，发现了 436 个与髋关节形态相关的 SNP，包括骨骼大小、结构和形状的变化。在 SNP 相关基因中，它对大小、骨骼结构和形状起着关键作用。总体而言，骨骼系统发育、细胞分化调节和软骨细胞分化是影响髋关节形态的关键过程。 GWAS 鉴定的与髋部形态相关的基因中有 18% 也与非髋部 OA 相关。我们的研究结果表明，髋部形态和 OA 之间存在多种共享的遗传机制，强调了在该领域进行更广泛研究的必要性，因为与髋部相比，膝部或足部形态的遗传背景在很大程度上仍未得到充分研究。