背景:先前的研究揭示了炎症性肠病(IBD)和脂溢性角化病(SK)之间的潜在联系。然而,这种关联是因果的还是混淆的仍然未知.
方法:我们进行了双样本孟德尔随机化(TSMR)分析,以阐明IBD之间的双向因果关系,包括其两种主要疾病克罗恩病(CD)和溃疡性结肠炎(UC),SK。IBD的遗传数据汇总,CD,UC和SK来自可访问的全基因组关联研究(GWAS)。这项TSMR研究主要使用逆方差加权(IVW)方法进行,由MR-Egger补充,加权中位数(WM),贝叶斯加权MR(BWMR),MR稳健调整后轮廓评分(MR-RAPS),MR-多效性残差和和离群值(MR-PRESSO),和径向IVWMR分析,使用修改的二阶权重(IVW[Mod2nd])方法。随后进行敏感性评估和潜在异常值的识别,以帮助解释结果。
结果:前向MR结果显示,IBD[比值比(OR)=1.068,95%置信区间(CI)=1.010-1.129,p=0.020)及其亚型CD(OR=1.088,95CI=1.038-1.139,p<0.001)增加了SK的风险。然而,SK的发生不受UC的影响(OR=1.090,95CI=0.977-1.216,p=0.123)。在反向分析中,SK与IBD无因果关系(OR=0.905,95CI=0.813-1.008,p=0.069),UC(OR=0.959,95CI=0.860-1.068,p=0.443),和CD(OR=0.933,95CI=0.846-1.029,p=0.165)。
结论:这些研究结果表明,IBD及其亚型CD可以增加欧洲人群中SK的发病率,而SK不影响IBD的发生。
BACKGROUND: Previous studies have revealed a potential link between inflammatory bowel disease (IBD) and seborrheic keratosis (SK). However, whether this association is causal or confounded remains unknown.
METHODS: We conducted this two-sample Mendelian randomization (TSMR) analysis to clarify bidirectional causality between IBD, including its two primary conditions Crohn\'s disease (CD) and ulcerative colitis (UC), and SK. The summary genetic data of IBD, CD, UC and SK were obtained from accessible genome-wide association studies (GWAS). This TSMR study was primarily performed using inverse-variance weighted (IVW) method, complemented by MR-Egger, weighted median (WM), Bayesian weighted MR (BWMR), MR-robust adjusted profile score (MR-RAPS), MR-pleiotropy residual sum and outlier (MR-PRESSO), and radial IVW MR analyses with modified second-order weights (IVW [Mod 2nd]) methods. Assessment of sensitivity and identification of potential outliers were subsequently conducted to aid interpretation of results.
RESULTS: The forward MR results showed that IBD [odds ratio (OR) = 1.068, 95% confidence interval (CI) = 1.010-1.129, p = 0.020) and its subtype CD (OR = 1.088, 95%CI = 1.038-1.139, p < 0.001) increased the risk of SK. However, the occurrence of SK could not be affected by UC (OR = 1.090, 95%CI = 0.977-1.216, p = 0.123). In the reverse analysis, no causal relationship between SK and IBD (OR = 0.905, 95%CI = 0.813-1.008, p = 0.069), UC (OR = 0.959, 95%CI = 0.860-1.068, p = 0.443), and CD (OR = 0.933, 95%CI = 0.846-1.029, p = 0.165) was identified.
CONCLUSIONS: These findings demonstrate that IBD and its subtype CD could increase the incidence of SK in European populations, whereas SK does not affect IBD occurrence.