Research Article: Tuber intake is independently associated with reduced risk of Hashimoto’s thyroiditis: a community-based cross-sectional study
Abstract:
Hashimoto’s thyroiditis (HT) is the leading cause of autoimmune hypothyroidism, and dietary factors have been implicated in its pathogenesis through immune and metabolic pathways. We aimed to identify dietary and metabolic factors associated with HT risk in a large community cohort and to evaluate whether tuber-associated metabolites causally influence HT susceptibility using Mendelian randomization (MR).
Cross-sectional analysis of 7,878 community-dwelling adults (?40 years) from the REACTION cohort, Dalian, China. HT was defined by thyroid autoantibody seropositivity (anti-TPO ?5.61 IU/mL or anti-Tg ?4.11 IU/mL). Forty-nine variables spanning dietary intake, lifestyle behaviours, anthropometrics, and metabolic parameters were screened by univariable and multivariable logistic regression. For MR, eight tuber-associated metabolites identified via the FoodB database were analysed as instrumental variable exposures against a published HT genome-wide association study (GWAS; N = 395,640; 15,654 cases) using inverse-variance weighted (IVW) as the primary method, with MR-Egger and weighted median as sensitivity analyses, and MR-PRESSO to assess and correct for horizontal pleiotropy.
HT prevalence was 29.3% (2,305/7,878). Female sex (OR 1.97, 95% CI 1.68 to 2.33), elevated total cholesterol (OR 1.13, 95% CI 1.02 to 1.26), and lower fasting glucose (OR 0.95, 95% CI 0.91 to 1.00) were independent metabolic predictors. Adequate tuber intake (50–100 g/day; OR 0.75, 95% CI 0.64 to 0.88; P = 0.001) and adequate vegetable intake (OR 0.87, 95% CI 0.79 to 0.96; P = 0.006) were independently protective, with tuber protection most pronounced in women (OR 0.76, 95% CI 0.63 to 0.90; P = 0.002). A dose–response analysis revealed a U-shaped pattern: adequate intake was protective (OR 0.77) while excessive intake (>100 g/day) was associated with increased risk (OR 1.50; P for trend = 0.45, non-significant linear trend). Four sensitivity analyses consistently confirmed the primary findings. In univariable MR, folic acid supplementation propensity was the only metabolite with adequate genetic instrumentation (mean F-statistic = 46.75; 736 harmonised SNPs). Genetically predicted folic acid supplement use causally increased HT risk across all three MR methods (IVW: ? = 0.105, SE = 0.001; P < 0.001; Weighted Median: ? = 0.112; P < 0.001), with outlier-robust analysis confirming a consistent estimate after removal of 74 influential SNPs (? = 0.109; effect change 4.1%).
Adequate tuber intake is an independent, novel protective dietary factor for HT, with a U-shaped dose–response pattern confirmed across four sensitivity analyses. Mendelian randomization identifies folic acid supplementation as a causal risk factor for HT, a finding with direct public health relevance given widespread supplement use in women of reproductive age. These findings support moderate tuber and vegetable consumption as a low-cost HT prevention strategy, and warrant caution regarding high-dose folic acid supplementation in HT-susceptible individuals.
Introduction:
Hashimoto’s thyroiditis (HT) is the leading cause of autoimmune hypothyroidism, and dietary factors have been implicated in its pathogenesis through immune and metabolic pathways. We aimed to identify dietary and metabolic factors associated with HT risk in a large community cohort and to evaluate whether tuber-associated metabolites causally influence HT susceptibility using Mendelian randomization (MR).
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