Causal association between obesity and hypothyroidism: a two-sample bidirectional Mendelian randomization study

Abstract

Introduction: Previous observational studies have reported a positive correlation between obesity and susceptibility to hypothyroidism; however, there is limited evidence from alternative methodologies to establish a causal link. Methods: We investigated the causal relationship between obesity and hypothyroidism using a two-sample bidirectional Mendelian randomization (MR) analysis. Single-nucleotide polymorphisms (SNPs) associated with obesity-related traits were extracted from a published genome-wide association study (GWAS) of European individuals. Summarized diagnostic data of hypothyroidism were obtained from the UK Biobank. Primary analyses were conducted using the inverse variance-weighted (IVW) method with a random-effects model as well as three complementary approaches. Sensitivity analyses were performed to ascertain the correlation between obesity and hypothyroidism. Results: MR analyses of the IVW method and the analyses of hypothyroidism/myxedema indicated that body mass index (BMI) and waist circumference (WC) were significantly associated with higher odds and risk of hypothyroidism. Reverse MR analysis demonstrated that a genetic predisposition to hypothyroidism was associated with an increased risk of elevated BMI and WC, which was not observed between WC adjusted for BMI (WCadjBMI) and hypothyroidism. Discussion: Our current study indicates that obesity is a risk factor for hypothyroidism, suggesting that individuals with higher BMI/WC have an increased risk of developing hypothyroidism and indicating the importance of weight loss in reducing the risk of hypothyroidism.