State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, 610041, China.
West China School of Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China.
BMC Oral Health. 2024 Mar 25;24(1):380. doi: 10.1186/s12903-024-04151-7.
Observational studies indicated a controversial relationship between periodontitis (PD) and Sjogren's syndrome (SS). To overcome restrictions in conventional observational studies, we conducted a two-sample Mendelian randomization (MR) analysis to assess the potential bidirectional relationship between PD and SS.
We utilized the largest available genome-wide association study (GWAS) of European ancestry on both PD (17,353 cases-28,210 controls) and SS (2495 cases-365,533 controls) for MR genetic instrument selection. The random-effect inverse-variance weighted (IVW) method complemented by Causal Analysis Using Summary Effect (CAUSE), weighted median, weighted mode, simple mode, MR-Egger regression, and MR-pleiotropy residual sum and outlier (MR-PRESSO) was used for MR analysis. Subsequent pleiotropy and heterogeneity tests were conducted.
IVW analysis exhibited neither an effect of PD on SS (OR = 0.939, 95%CI = 0.525-1.677, P = 0.8304) nor that of SS on PD (OR = 1.007, 95%CI = 0.977-1.038, P = 0.6440). The other five complementary methods further recognized the null association with an effect size close to one. No significant pleiotropy was detected in the relationship between PD and SS (P > 0.05). Heterogeneity existed in the effect of PD on SS but not vice versa.
No genetic causality between PD and SS or vice versa was supported by our results under MR assumptions and limitations. The study results provided new insights into the relationship between periodontal status and sjogren's syndrome, highlighting the need for a more prudent medical intervention.
观察性研究表明，牙周炎（PD）和干燥综合征（SS）之间存在争议的关系。为了克服常规观察性研究的限制，我们进行了两样本孟德尔随机化（MR）分析，以评估 PD 和 SS 之间潜在的双向关系。
我们利用最大的欧洲裔人群全基因组关联研究（GWAS），对 PD（17353 例病例-28210 例对照）和 SS（2495 例病例-365533 例对照）进行 MR 遗传工具选择。随机效应逆方差加权（IVW）方法，辅以因果分析使用汇总效应（CAUSE）、加权中位数、加权模式、简单模式、MR-Egger 回归和 MR 偏倚残差和异常值（MR-PRESSO），用于 MR 分析。随后进行了偏倚和异质性检验。
IVW 分析显示，PD 对 SS 没有影响（OR=0.939，95%CI=0.525-1.677，P=0.8304），SS 对 PD 也没有影响（OR=1.007，95%CI=0.977-1.038，P=0.6440）。其他五种补充方法进一步证实了这种接近 1 的效应大小的零关联。在 PD 和 SS 之间的关系中没有发现显著的偏倚（P>0.05）。在 PD 对 SS 的影响中存在异质性，但反之则不然。
在 MR 假设和限制下，我们的研究结果不支持 PD 和 SS 之间或反之存在遗传因果关系。研究结果为牙周状况与干燥综合征之间的关系提供了新的见解，强调需要更谨慎的医疗干预。
