Han Tian, Han Xiaosong, Liu Liu, Wang Yuliang, Peng Xiaoliao, Zhou Xingtao
Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China.
NHC Key Laboratory of Myopia (Fudan University), Shanghai, China.
Cornea. 2025 Mar 1;44(3):300-304. doi: 10.1097/ICO.0000000000003736.
The relationship between keratoconus (KC) and osteoarthritis (OA) has been hypothesized, yet the causal link remained obscure. We aimed to evaluate the genetic correlation and causality between KC and OA through a genetic perspective.
Linkage Disequilibrium Score Regression and bidirectional 2-sample Mendelian randomization (MR) analysis were conducted. Data were used from genome-wide association study on KC (4669 cases and 116,547 controls), OA (encompassing 24,955 patients with knee OA, 15,704 patients with hip OA, 39,427 patients with knee or hip OA, and 378,169 control participants), and KC data in the FinnGen consortium for replication and meta-analysis. Simple model, weighted model, inverse-variance weighted, weighted median, and MR-Egger regression were employed to assess the causal effects. MR pleiotropy residual sum and outlier method, MR-Egger method, and leave-one-out analysis were also applied to detect pleiotropy.
No statistically significant genetic correlation between KC and OA (all P > 0.05) were observed. MR estimates obtained from all 5 methods after meta-analysis revealed nonsignificant odds ratio values of KC-related traits to knee OA, hip OA, and OA (all adjusted P > 0.05). No evidence of causal relationships of knee and hip OA with KC-related traits was detected after meta-analysis of all 5 MR methods (all adjusted P > 0.05).
The large MR analysis indicated that KC may not be causally associated with a risk of OA.
圆锥角膜（KC）与骨关节炎（OA）之间的关系已被提出假设，但因果联系仍不明确。我们旨在从遗传学角度评估KC与OA之间的遗传相关性和因果关系。
进行连锁不平衡评分回归和双向双样本孟德尔随机化（MR）分析。数据来自KC的全基因组关联研究（4669例患者和116547名对照）、OA（包括24955例膝关节OA患者、15704例髋关节OA患者、39427例膝关节或髋关节OA患者以及378169名对照参与者），以及芬兰基因库联盟中的KC数据用于重复验证和荟萃分析。采用简单模型、加权模型、逆方差加权、加权中位数和MR-Egger回归来评估因果效应。还应用MR多效性残差和异常值方法、MR-Egger方法以及留一法分析来检测多效性。
未观察到KC与OA之间存在统计学显著的遗传相关性（所有P>0.05）。荟萃分析后从所有5种方法获得的MR估计显示，KC相关性状与膝关节OA、髋关节OA和OA的比值比无统计学意义（所有校正P>0.05）。对所有5种MR方法进行荟萃分析后，未检测到膝关节和髋关节OA与KC相关性状之间存在因果关系的证据（所有校正P>0.05）。
大规模MR分析表明，KC可能与OA风险无因果关联。
