PDF(Pubmed)
Abstract：
BACKGROUND: Previous observational studies have shown that vitiligo usually co-manifests with a variety of dysglycemic diseases, such as Type 1 diabetes mellitus (T1DM) and Type 2 diabetes mellitus (T2DM). Mendelian randomization (MR) analysis was performed to further evaluate the causal association between fasting plasma glucose, glycosylated hemoglobin (HbA1c), T1DM, T2DM and vitiligo.
METHODS: We used aggregated genome-wide association data from the Integrative Epidemiology Unit (IEU) online database of European adults vitiligo; HbA1c data were from IEU. Fasting blood glucose data were obtained from the European Bioinformatics Institute (EBI). T1DM and T2DM data were from FinnGen. We used bidirectional two-sample and multivariate MR analyses to test whether dysglycemic measures (fasting blood glucose, HbA1c), diabetes-related measures (T1DM, T2DM) are causatively associated with vitiligo. Inverse variance weighting (IVW) method was used as the main test method, MR-Egger, Weighted mode and Weighted median were used as supplementary methods.
RESULTS: We found no statistically significant evidence to support a causal association between dysglycemic traits and vitiligo, but in the correlation analysis of diabetic traits, our data supported a positive causal association between T1DM and vitiligo (p = 0.018). In the follow-up multivariate MR analysis, our results still supported this conclusion (p = 0.016), and suggested that HbA1c was not a mediator of T1DM affecting the pathogenesis of vitiligo. No reverse causality was found in any of the reverse MR Analyses of dysglycemic traits and diabetic traits.
CONCLUSIONS: Our findings support that T1DM is a risk factor for the development of vitiligo, and this conclusion may explain why the co-presentation of T1DM and vitiligo is often seen in observational studies. Clinical use of measures related to T1DM may be a new idea for the prevention or treatment of vitiligo.
METHODS: We used aggregated genome-wide association data from the Integrative Epidemiology Unit (IEU) online database of European adults vitiligo; HbA1c data were from IEU. Fasting blood glucose data were obtained from the European Bioinformatics Institute (EBI). T1DM and T2DM data were from FinnGen. We used bidirectional two-sample and multivariate MR analyses to test whether dysglycemic measures (fasting blood glucose, HbA1c), diabetes-related measures (T1DM, T2DM) are causatively associated with vitiligo. Inverse variance weighting (IVW) method was used as the main test method, MR-Egger, Weighted mode and Weighted median were used as supplementary methods.
RESULTS: We found no statistically significant evidence to support a causal association between dysglycemic traits and vitiligo, but in the correlation analysis of diabetic traits, our data supported a positive causal association between T1DM and vitiligo (p = 0.018). In the follow-up multivariate MR analysis, our results still supported this conclusion (p = 0.016), and suggested that HbA1c was not a mediator of T1DM affecting the pathogenesis of vitiligo. No reverse causality was found in any of the reverse MR Analyses of dysglycemic traits and diabetic traits.
CONCLUSIONS: Our findings support that T1DM is a risk factor for the development of vitiligo, and this conclusion may explain why the co-presentation of T1DM and vitiligo is often seen in observational studies. Clinical use of measures related to T1DM may be a new idea for the prevention or treatment of vitiligo.
摘要：
背景：以前的观察性研究表明，白癜风通常与多种血糖异常疾病共同表现，如1型糖尿病（T1DM）和2型糖尿病（T2DM）。进行孟德尔随机化(MR)分析以进一步评估空腹血糖之间的因果关系,糖化血红蛋白（HbA1c），T1DM,T2DM和白癜风。
方法：我们使用了来自欧洲成人白癜风综合流行病学单位（IEU）在线数据库的全基因组关联汇总数据；HbA1c数据来自IEU。空腹血糖数据从欧洲生物信息学研究所(EBI)获得。T1DM和T2DM数据来自FinnGen。我们使用双向双样本和多变量MR分析来测试血糖是否异常测量(空腹血糖，HbA1c），糖尿病相关措施（T1DM，T2DM）与白癜风有因果关系。采用逆方差加权(IVW)方法作为主要检验方法，MR-Egger,使用加权模式和加权中位数作为补充方法。
结果：我们没有发现统计学上显著的证据支持血糖异常特征与白癜风之间的因果关系，但是在糖尿病性状的相关性分析中，我们的数据支持T1DM和白癜风之间存在正的因果关系(p=0.018).在后续的多变量MR分析中，我们的结果仍然支持这一结论(p=0.016)，提示HbA1c不是T1DM影响白癜风发病的介质。在血糖异常性状和糖尿病性状的任何反向MR分析中均未发现反向因果关系。
结论：我们的研究结果支持T1DM是白癜风发展的危险因素，这一结论可以解释为什么在观察性研究中经常看到T1DM和白癜风的共同表现。临床应用T1DM相关措施可能为白癜风的预防或治疗提供新的思路。
方法：我们使用了来自欧洲成人白癜风综合流行病学单位（IEU）在线数据库的全基因组关联汇总数据；HbA1c数据来自IEU。空腹血糖数据从欧洲生物信息学研究所(EBI)获得。T1DM和T2DM数据来自FinnGen。我们使用双向双样本和多变量MR分析来测试血糖是否异常测量(空腹血糖，HbA1c），糖尿病相关措施（T1DM，T2DM）与白癜风有因果关系。采用逆方差加权(IVW)方法作为主要检验方法，MR-Egger,使用加权模式和加权中位数作为补充方法。
结果：我们没有发现统计学上显著的证据支持血糖异常特征与白癜风之间的因果关系，但是在糖尿病性状的相关性分析中，我们的数据支持T1DM和白癜风之间存在正的因果关系(p=0.018).在后续的多变量MR分析中，我们的结果仍然支持这一结论(p=0.016)，提示HbA1c不是T1DM影响白癜风发病的介质。在血糖异常性状和糖尿病性状的任何反向MR分析中均未发现反向因果关系。
结论：我们的研究结果支持T1DM是白癜风发展的危险因素，这一结论可以解释为什么在观察性研究中经常看到T1DM和白癜风的共同表现。临床应用T1DM相关措施可能为白癜风的预防或治疗提供新的思路。
