Assessing Causal Relationships Between Diabetes Mellitus and Idiopathic Pulmonary Fibrosis
Assessing Causal Relationships Between Diabetes Mellitus and Idiopathic Pulmonary Fibrosis
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DOI：
10.1101/2024.01.04.24300827
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发表时间：
2024-01
期刊：
影响因子：
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通讯作者：
Samuel Moss;Cosetta Minelli;O. Leavy;R. Allen;Nick Oliver;L. Wain;Gisli Jenkins;Iain Stewart;Mr. Samuel Moss;Margaret Turner Warwick
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文献类型：
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作者：
Samuel Moss;Cosetta Minelli;O. Leavy;R. Allen;Nick Oliver;L. Wain;Gisli Jenkins;Iain Stewart;Mr. Samuel Moss;Margaret Turner Warwick
依据：特发性肺纤维化（IPF）是一种进行性肺瘢痕形成疾病。已知IPF与糖尿病（DM）之间存在相关性，但尚不清楚这种相关性是否是由于这些特征之间的因果关系所致。目的：使用孟德尔随机化方法检查DM、糖尿病相关特征和IPF之间的因果关系。研究方法：遵循双样本孟德尔随机化（MR）方法，我们使用从1型糖尿病（T1D）、2型糖尿病（T2D）、糖化血红蛋白水平（HbA1c）、空腹胰岛素水平和体重指数（BMI）的全基因组关联研究（GWAS）中鉴定的遗传变异，以评估这些特征对IPF风险的因果影响的证据。使用多效性稳健和多变量MR方法进行进一步分析，以解释所研究性状的固有复杂性。结果如下：结果未表明T1D（OR = 1.00，95% CI：0.93 - 1.07，p = 0.902）或T2D（OR = 1.02，95% CI：0.93 - 1.11，p = 0.692）是IPF的致病途径。提示HbA1c无显著影响（OR = 1.19，95% CI：0.63 - 2.22，p = 0.592）或空腹胰岛素水平（OR = 0.60，95% CI：0.31 - 1.15，p = 0.124），但BMI对IPF风险的影响也显示出来（OR = 1.44，95% CI：1.12 - 1.85，p = 0.004）。结论：本研究表明，DM和IPF不太可能存在因果关系。这种共病关系可能是由共同的风险因素或治疗效果驱动的。
Rationale: Idiopathic Pulmonary Fibrosis (IPF) is a disease of progressive lung scarring. There is a known association between IPF and diabetes mellitus (DM), but it is unclear whether this association is due to causal relationships between these traits. Objectives: To examine causal relationships between DM, diabetes-associated traits, and IPF using a Mendelian randomisation approach. Methods: Following a two-sample Mendelian randomisation (MR) approach, we used genetic variants identified from genome wide association studies (GWAS) for type 1 diabetes (T1D), type 2 diabetes (T2D), glycated haemoglobin level (HbA1c), fasting insulin level, and body mass index (BMI) to assess for evidence of causal effects of these traits on IPF risk. Further analyses using pleiotropy-robust and multivariable MR methods were performed to account for the inherent complexity of the traits being investigated. Results: Results did not suggest that either T1D (OR = 1.00, 95% CI: 0.93-1.07, p = 0.902) or T2D (OR = 1.02, 95% CI: 0.93-1.11, p = 0.692) are in the causal pathway of IPF. No significant effects were suggested of HbA1c (OR = 1.19, 95% CI: 0.63-2.22, p = 0.592) or fasting insulin level (OR = 0.60, 95% CI: 0.31-1.15, p = 0.124) on IPF risk, but effects of BMI on IPF risk were indicated (OR = 1.44, 95% CI: 1.12-1.85, p = 0.004). Conclusion: This study suggests that DM and IPF are unlikely to be causally linked. This comorbid relationship may instead be driven by shared risk factors or treatment effects.