Clinical Research

The relationship between ulcerative colitis and the risk of hypothyroidism: A two⁃mendelian randomization study

  • Yin HUA ,
  • Xiaoyan WANG ,
  • Zhen WANG ,
  • Yongning XIN ,
  • Shousheng. LIU
Expand
  • *.Qingdao Clinical Medical College Affiliated to Nanjing Medical University (Qingdao Municipal Hospital),Qingdao 266011,China

Received date: 2023-11-28

  Online published: 2024-04-08

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.

Cite this article

Yin HUA , Xiaoyan WANG , Zhen WANG , Yongning XIN , Shousheng. LIU . The relationship between ulcerative colitis and the risk of hypothyroidism: A two⁃mendelian randomization study[J]. The Journal of Practical Medicine, 2024 , 40(6) : 827 -832 . DOI: 10.3969/j.issn.1006-5725.2024.06.016

References

1 SEGAL J P, LEBLANC J F, HART A L. Ulcerative colitis: an update [J]. Clin Med (Lond), 2021, 21(2): 135-139. doi:10.7861/clinmed.2021-0080
2 LAMB C A, KENNEDY N A, RAINE T, et al. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults [J]. Gut, 2019, 68(): s1-s106. doi:10.1136/gutjnl-2019-318484
3 JANSEN H I, BOELEN A, HEIJBOER A C, et al. Hypothyroidism: The difficulty in attributing symptoms to their underlying cause [J]. Front Endocrinol (Lausanne), 2023,14:1130661. doi:10.3389/fendo.2023.1130661
4 RALLI M, ANGELETTI D, FIORE M, et al. Hashimoto's thyroiditis: An update on pathogenic mechanisms, diagnostic protocols, therapeutic strategies, and potential malignant transformation [J]. Autoimmun Rev, 2020,19(10):102649. doi:10.1016/j.autrev.2020.102649
5 HUGHES K, EASTMAN C. Thyroid disease: Long-term management of hyperthyroidism and hypothyroidism[J]. Aust J Gen Pract, 2021,50(1):36-42. doi:10.31128/ajgp-09-20-5653
6 VIRILI C, STRAMAZZO I, SANTAGUIDA M G, et al. Ulcerative Colitis as a Novel Cause of Increased Need for Levothyroxine [J]. Front Endocrinol (Lausanne), 2019,10:233. doi:10.3389/fendo.2019.00233
7 KAPPELMAN M D, GALANKO J A, PORTER C Q, et al. Association of paediatric inflammatory bowel disease with other immune-mediated diseases [J]. Arch Dis Child, 2011, 96(11): 1042-1046. doi:10.1136/archdischild-2011-300633
8 MAHMOUD A A, ABDELHAY A, KHAMIS A, et al. Hemophagocytic lymphohistiocytosis in inflammatory bowel disease: a nationwide analysis [J]. Ann Hematol, 2023, 102(7): 1705-1711. doi:10.1007/s00277-023-05223-4
9 YAKUT M, üSTüN Y, KABACAN G, et al. Thyroid Disorders in Patients with Inflammatory Bowel Diseases [J]. Int J Clin Med, 2011,2(2):89-92.
10 DORE M P, FANCIULLI G, MANCA A, et al. Clinically relevant thyroid disorders and inflammatory bowel disease are inversely related: a retrospective case-control study [J]. Scand J Gastroenterol, 2021, 56(2): 171-176. doi:10.1080/00365521.2020.1861323
11 任首泽,李泽光,李林蔚,等.自身免疫性疾病与甲状腺功能障碍的孟德尔随机化研究[J].预防医学,2023,35(12):1024-1028.
12 BURGESS S, DAVEY SMITH G, DAVIES N M, et al. Guidelines for performing Mendelian randomization investigations: update for summer 2023 [J]. Wellcome Open Res, 2023, 4:186. doi:10.12688/wellcomeopenres.15555.3
13 ONGJ S, MACGREGOR S. Implementing MR-PRESSO and GCTA-GSMR for pleiotropy assessment in Mendelian randomization studies from a practitioner's perspective [J]. Genet Epidemiol, 2019, 43(6): 609-616. doi:10.1002/gepi.22207
14 PAPADIMITRIOU N, DIMOU N, TSILIDIS K K, et al. Physical activity and risks of breast and colorectal cancer: a Mendelian randomisation analysis [J]. Nat Commun, 2020,11(1):597.
15 HAYCOCK P C, BURGESS S, WADE K H, et al. Best (but oft-forgotten) practices: the design, analysis, and interpretation of Mendelian randomization studies [J]. Am J Clin Nutr, 2016, 103(4): 965-978. doi:10.3945/ajcn.115.118216
16 KNAUS U G. Oxidants in Physiological Processes[J]. Handb Exp Pharmacol,2021,264:27-47. doi:10.1007/164_2020_380
17 LIU M, LUO P, LIU L, et al. Immune-mediated inflammatory diseases and leukocyte telomere length: A Mendelian randomization study[J]. Front Genet,2023,14:1129247. doi:10.3389/fgene.2023.1129247
18 CASELLA G, DE MARCO E, ANTONELLI E, et al. The prevalence of hyper- and hypothyroidism in patients with ulcerative colitis [J]. J Crohns Colitis, 2008, 2(4): 327-330. doi:10.1016/j.crohns.2008.09.001
19 RICART E, PANACCIONE R, LOFTUS E V, et al. Autoimmune disorders and extraintestinal manifestations in first-degree familial and sporadic inflammatory bowel disease: a case-control study [J]. Inflamm Bowel Dis, 2004, 10(3): 207-214. doi:10.1097/00054725-200405000-00005
20 POORAN N, SINGH P, BANK S. Crohn's disease and risk of fracture: does thyroid disease play a role? [J]. World J Gastroenterol, 2003, 9(3): 615-618. doi:10.3748/wjg.v9.i3.615
21 YEHUDA S BAR, AXLEROD R, TOKER O, et al. The Association of Inflammatory Bowel Diseases with Autoimmune Disorders: A Report from the epi-IIRN [J]. J Crohns Colitis, 2019, 13(3): 324-349. doi:10.1093/ecco-jcc/jjy166
22 PASCHOU S A, PALIOURA E, KOTHONAS F, et al. The effect of anti-TNF therapy on thyroid function in patients with inflammatory bowel disease [J]. Endocr J, 2018, 65(11): 1121-1125. doi:10.1507/endocrj.ej18-0243
Outlines

/