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Generation of a Mouse Spontaneous Autoimmune Thyroiditis Model
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The Causal Effects of Primary Biliary Cholangitis on Thyroid Dysfunction: A Two-Sample Mendelian Randomization Study.

Peng Huang1, Yuqing Hou1, Yixin Zou1

  • 1Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.

Frontiers in Genetics
|December 27, 2021
PubMed
Summary

Primary biliary cholangitis (PBC) increases the risk of autoimmune thyroid disease (AITD), hypothyroidism, and thyroid cancer. Autoimmune thyroid disease also shows a potential causal link to PBC, offering new insights into PBC

Keywords:
genome-wide association studyhypothyroidismthyroid cancerthyroid dysfunctiontwo-sample Mendelian randomization

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Area of Science:

  • Genetics
  • Immunology
  • Endocrinology

Background:

  • Primary biliary cholangitis (PBC) is an autoimmune liver disease frequently associated with thyroid dysfunction.
  • Understanding the causal link between PBC and thyroid disorders is crucial for elucidating PBC pathogenesis and managing its complications.

Purpose of the Study:

  • To investigate the potential causal relationship between primary biliary cholangitis (PBC) and various thyroid dysfunctions using Mendelian randomization.
  • To assess the impact of PBC on autoimmune thyroid disease (AITD), thyroid-stimulating hormone (TSH), free thyroxine (FT4), hyperthyroidism, hypothyroidism, and thyroid cancer (TC).

Main Methods:

  • Employed a two-sample Mendelian randomization (MR) approach utilizing seven European population datasets.
  • Conducted extensive sensitivity analyses to ensure the robustness and reliability of the causal estimations.

Main Results:

  • Primary biliary cholangitis (PBC) was identified as a risk factor for autoimmune thyroid disease (AITD) (OR=1.002), elevated TSH (OR=1.016), hypothyroidism (OR=1.068), and thyroid cancer (TC) (OR=1.106).
  • Reverse-direction MR analysis indicated a significant potential causal association between AITD and PBC (OR=0.021), with no significant causal relation found in the other direction for AITD or TC.

Conclusions:

  • Primary biliary cholangitis (PBC) causally influences thyroid dysfunction, specifically increasing the risk of AITD, mild hypothyroidism, and thyroid cancer.
  • The identified bidirectional causal relationship between PBC and thyroid dysfunction provides novel perspectives on the etiology of PBC and its associated conditions.