Maternal Smoking Around Birth Is a Risk Factor for Gastrointestinal Diseases in Offspring: A Mendelian Randomization Study.

Background: The effect of maternal smoking around birth (MSAB) on gastrointestinal (GI) diseases in the offspring is still not fully understood.

Aim: We conducted a rigorous Mendelian randomization (MR) study to examine the association between MSAB and 24 GI diseases in offspring.

Methods: Single nucleotide polymorphisms (SNPs) associated with MSAB were obtained from a recent study. SNPs of GI diseases were all from the FinnGen project. We performed two-sample MR analyses (TSMR) using three methods, predominantly the inverse variance weighting (IVW) method. We performed sensitivity analyses and false discovery rate (FDR) to confirm the accuracy and robustness of the results.

Results: Genetically determined MSAB significantly influenced offspring GI diseases according to the IVW method (OR 1.251; 95% CI 1.111-1.408; P = 2.111e-04; P_FDR = 5.278e-03). We then found that genetic predisposition to MSAB was significantly associated with an increased risk of 5 of 24 GI diseases, including three upper GI diseases (esophageal ulcer, gastroduodenal ulcer, and its subtype gastroduodenal ulcer) and two lower GI diseases (inflammatory bowel disease (IBD) and its subtype, ulcerative colitis (UC)) in offspring.

Conclusions: This comprehensive TSMR analysis demonstrated that genetically predicted MSAB is a risk factor for GI disorders, including IBD, UC, and peptic ulcer, in offspring. Individuals whose mothers smoked during pregnancy are subject to increased health surveillance for GI diseases. And we need more research to explore the mediating mechanisms involved.