University of Augsburg, University Hospital Augsburg, Stenglinstr. 2, 86156, Augsburg, Germany.
Institute for Medical Information Processing, Biometry, and Epidemiology, Ludwig-Maximilians-Universität München, Munich, Germany.
BMC Med. 2022 Mar 16;20(1):82. doi: 10.1186/s12916-022-02283-7.
The question of whether asthma is causally related to gastrointestinal disorders remained unanswered so far. Thus, this study investigated whether there is such a relation and whether the time of onset of asthma plays a role in the occurrence of the following gastrointestinal disorders: peptic ulcer disease (PUD), gastroesophageal reflux disease (GORD), irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD) including the distinction between Crohn's disease (CD) and ulcerative colitis (UC).
Using summary data of genome-wide association studies (GWASs), we ran Mendelian randomization analyses based on up to 456,327 European participants. Outlier assessment, a series of sensitivity analyses and validation of IBD results in a second GWAS were performed to confirm the results.
Presented ORs represent the average change in the outcome per 2.72-fold increase in the prevalence of the exposure. Genetically predicted childhood-onset asthma was positively associated with PUD, GORD, and IBS with similar odds ratios near 1.003 and adjusted P-values from 0.007 (GORD) to 0.047 (PUD). Furthermore, it was inversely related to IBD (OR = 0.992, 95% CI: 0.986, 0.998, adjusted P = 0.023) and suggestively associated with its UC subtype (OR = 0.990, 95% CI: 0.982, 0.998, adjusted P = 0.059). There were no associations between genetically predicted adult-onset asthma and the mentioned gastrointestinal disorders.
This study provides evidence that the presence of asthma onset in childhood increases the risk for GORD, PUD, and IBS but decreases the risk for IBD in adults. The lower risk for IBD may be attributed to a lower risk primarily for UC.
哮喘是否与胃肠道疾病有因果关系，至今仍未得到解答。因此，本研究旨在探讨两者之间是否存在关联，以及哮喘的发病时间是否会影响以下胃肠道疾病的发生：消化性溃疡病（PUD）、胃食管反流病（GORD）、肠易激综合征（IBS）和炎症性肠病（IBD），包括克罗恩病（CD）和溃疡性结肠炎（UC）的区分。
本研究使用全基因组关联研究（GWAS）的汇总数据，对多达 456327 名欧洲参与者进行了基于孟德尔随机化的分析。通过异常值评估、一系列敏感性分析以及对第二次 GWAS 中 IBD 结果的验证，以确认结果。
呈现的比值比代表了每增加 2.72 倍的暴露患病率，结局的平均变化。儿童期起病的哮喘的遗传预测与 PUD、GORD 和 IBS 呈正相关，比值比接近 1.003，调整后的 P 值从 0.007（GORD）到 0.047（PUD）。此外，它与 IBD 呈负相关（OR=0.992，95%CI：0.986，0.998，调整后的 P=0.023），并且与 UC 亚型呈提示性相关（OR=0.990，95%CI：0.982，0.998，调整后的 P=0.059）。遗传预测的成人起病的哮喘与上述胃肠道疾病之间没有关联。
本研究提供了证据表明，儿童期起病的哮喘会增加成年后 GORD、PUD 和 IBS 的发病风险，但会降低成年后 IBD 的发病风险。IBD 风险降低可能归因于 UC 的发病风险降低。
