Epidemiological studies have consistently shown that Sjögren’s disease (SjD) increases the risk of dental caries. Despite similar evidence indicating an elevated risk of periodontitis, SjD remains a disputed risk factor for this disease. The risk of bias in observational research is a major impediment to confirming this link. Within an instrumental variable framework, genetic variants associated with a risk factor can be used to proxy its effect on an outcome while avoiding common sources of observational study bias. In this study, we leveraged an instrumental variable approach to investigate whether SjD affects the risk of caries and periodontitis. A total of 57 genetic variants strongly associated with SjD were identified from a genome-wide association study of 2,247 European descent cases and 332,115 controls. We tested for associations of these genetic instruments with caries (measured as the number of decayed, missing, and filled surfaces in 26,792 individuals) and periodontitis (17,353 clinical periodontitis cases and 28,210 European controls). Several sensitivity analyses were used to further validate the primary inverse variance weighted (IVW) estimate. IVW analysis revealed an adverse effect of SjD on caries (β = 0.039, P = 6.3e-16) and periodontitis (odds ratio = 1.033, P = 2.3e-05). Sensitivity analyses, conducted to assess the robustness to potential violations of instrumental variable assumptions, further support these findings. Our results showed that SjD has a detrimental effect on caries and also suggest that SjD promotes periodontitis.

中文翻译：

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干燥病与口腔健康：遗传工具变量分析

流行病学研究一致表明，干燥病 (SjD) 会增加龋齿的风险。尽管类似的证据表明牙周炎的风险升高，但牙周病仍然是这种疾病的一个有争议的危险因素。观察性研究中的偏见风险是确认这种联系的主要障碍。在工具变量框架内，与风险因素相关的遗传变异可用于代理其对结果的影响，同时避免观察性研究偏差的常见来源。在这项研究中，我们利用工具变量方法来研究 SjD 是否会影响龋齿和牙周炎的风险。对 2,247 名欧洲血统病例和 332,115 名对照者进行的全基因组关联研究中，鉴定出总共 57 个与 SjD 密切相关的遗传变异。我们测试了这些遗传工具与龋齿（以 26,792 名个体中腐烂、缺失和填充表面的数量来衡量）和牙周炎（17,353 名临床牙周炎病例和 28,210 名欧洲对照）之间的关联。使用多项敏感性分析来进一步验证主要逆方差加权 (IVW) 估计。IVW 分析显示 SjD 对龋齿（β = 0.039，P = 6.3e-16）和牙周炎（比值比 = 1.033，P = 2.3e-05）有不良影响。为评估工具变量假设的潜在违反的稳健性而进行的敏感性分析进一步支持了这些发现。我们的结果表明，SjD 对龋齿有不利影响，并且还表明 SjD 会促进牙周炎。