目的:了解髋关节疾病的发病机制,如骨关节炎(OA),对推进他们的治疗至关重要。此类髋部疾病通常涉及特定的形态变化。遗传变异,叫做SNPs,影响各种髋关节形态参数。这项研究调查了全基因组关联研究(GWAS)中与髋关节形态相关的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,旨在观察相同的基因是否在髋关节发育和其他下肢关节OA的风险中发挥作用。
方法:进行了系统的文献综述,以确定与髋关节形态相关的SNP,基于人口,干预,比较,结果,和研究(PICOS)框架。之后,进行基因本体论(GO)分析,使用EnrichR,在SNP相关基因上,并与非髋部OA相关基因进行比较,跨不同的数据库。
结果:审查49个GWAS确定了436个与髋关节形态相关的SNP,包括骨骼大小的变化,结构和形状。在SNP相关基因中,SOX9在尺寸方面起着举足轻重的作用,GDF5影响骨骼结构,和BMP7影响形状。总的来说,骨骼系统发育,细胞分化的调节,软骨细胞分化是影响髋关节形态的关键过程。18%的GWAS鉴定的与髋关节形态相关的基因也与非髋关节OA相关。
结论:我们的研究结果表明,髋关节形态和OA存在多种共有的遗传机制,强调在这一领域进行更广泛研究的必要性,与臀部相比,膝盖或脚形态的遗传背景仍未得到充分研究。
OBJECTIVE: 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.
METHODS: 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.
RESULTS: Reviewing 49 GWAS identified 436 SNPs associated with hip joint morphology, encompassing variance in bone size, structure and shape. Among the SNP-associated genes, SOX9 plays a pivotal role in size, GDF5 impacts bone structure, and BMP7 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.
CONCLUSIONS: 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.