Abstract:

Objective To investigate assess the bidirectional causal relationship between ulcerative colitis （UC） and hypothyroidism using a two?sample Mendelian randomization （TSMR）. Methods Single nucleotide polymorphism （SNP） data relevant to UC and hypothyroidism were retrieved from the Finnish Biobank and the IEU database， respectively. Independent SNPs strongly associated with UC were selected as instrumental variables. Causal associations between UC and hypothyroidism were evaluated using the inverse variance weighted （IVW） method， MR?Egger regression， and weighted median estimator. Additionally， MR?PRESSO was employed to assess the horizontal pleiotropy and outlier SNPs. Cochran′s Q test and funnel plots were performed to evaluate the heterogeneity among the SNPs. A leave?one?out analysis was conducted to examine the influence of individual SNPs on causal assessments. Results Four instrumental variables strongly associated with UC were identified. The IVW method indicated a causal relationship between UC and hypothyroidism （OR = 0.975， 95% CI： 0.924 ~ 0.990， P = 0.011）. Cochran′s Q test yielded a Q statistic of 2.566 with a p?value of 0.463， suggesting no heterogeneity among the SNPs. Both MR?Egger （P = 0.523） and MR?PRESSO （P = 0.548） tests suggested the absence of horizontal pleiotropy. However， the results of the reverse TSMR did not support a reverse causal relationship. Conclusion The findings from the TSMR analysis reveal a negative causal relationship between UC and hypothyroidism.

Key words: ulcerative colitis, hypothyroidism, mendelian randomization