Abstract
INTRODUCTION: This study aimed to investigate the association between maternal smoking around birth and the incidence of offspring constipation. METHODS: Genome-wide association study (GWAS) data for maternal smoking around birth and offspring constipation were obtained from the Mendelian randomization (MR) Base platform. Single nucleotide polymorphisms (SNPs) significantly associated with maternal smoking around birth were utilized as instrumental variables in two-sample MR analyses to explore the relationship between maternal smoking and offspring constipation. The analytical methods employed included the inverse-variance weighted (IVW) method, weighted median estimator, and MR-Egger regression. RESULTS: Twenty SNPs significantly associated with maternal smoking around birth (p<5×10(-8); linkage disequilibrium r(2)<0.001) were identified. Across the different methods, a consistent positive association was observed between maternal smoking around birth and an increased risk of constipation in offspring (IVW: OR=4.35; 95% CI: 1.81-10.45; weighted median estimator: OR=4.23; 95% CI: 1.22-14.75; MR-Egger: OR=0.92; 95% CI: 0.01-122.07), suggesting that higher frequency of maternal smoking is associated with an elevated risk of constipation in offspring. However, we did not detect any potential effect of genetic liability to constipation risk on maternal smoking. CONCLUSIONS: This study provides evidence suggesting that increased maternal smoking around the time of birth may be linked to a higher risk of constipation in offspring.