Association between autoimmune diseases and thyroid dysfuction: a Mendelian randomization study
REN Shouze1, LI Zeguang2, LI Linwei3, XIA Kaiyu1, LIANG Hua1
1. Department of Basic Medical Sciences, Heilongjiang University of Traditional Chinese Medicine, Harbin, Heilongjiang 150040, China; 2. The First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, Heilongjiang 150040, China; 3. Heilongjiang Provincial Hospital, Harbin, Heilongjiang 150040, China
Abstract:Objective To evaluate the association between autoimmune diseases (ADs) and thyroid dysfunction using a Mendelian randomization (MR) approach. Methods Genetic predictors of hypothyroidism and hyperthyroidism were collected through the UK Biobank, including 337 159 individuals and 10 894 596 single nucleotide polymorphisms (SNPs). Genetic predictors of 6 ADs including systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), type 1 diabetes mellitus (T1DM), rheumatoid arthritis (RA), primary biliary cholangitis (PBC), and multiple sclerosis (MS) were collected through the GWAS Catalog database, including 14 267 individuals and 7 071 163 SNPs, 22 647 individuals and 99 962 SNPs, 24 840 individuals and 12 783 129 SNPs, 58 284 individuals and 13 108 512 SNPs, 13 239 individuals and 1 124 241 SNPs, and 38 589 individuals and 156 632 SNPs. MR analysis was performed using the inverse-variance weighted (IVW) method. The horizontal pleiotropy was assessed using the MR-Egger regression, and sensitivity analysis was conducted with the leave-one-out. Results IVW results showed that a higher risk of hypothyroidism was associated with T1DM (OR=1.007, 95%CI: 1.003-1.011, P<0.05), SLE (OR=1.005, 95%CI: 1.002-1.009, P<0.05), and RA (OR=1.013, 95%CI: 1.009-1.016, P<0.05); a higher risk of hyperthyroidism was associated with T1DM (OR=1.002, 95%CI: 1.001-1.003, P<0.05) and SLE (OR=1.002, 95%CI: 1.001-1.003, P<0.05). Conclusions Genetically predicted ADs are associated with an increased risk of thyroid dysfunction. A higher risk of hypothyroidism is associated with T1DM, SLE and RA; a higher risk of hyperthyroidism is associated with T1DM and SLE.
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