Thyroid Function and Metabolic Syndrome: A Two-Sample Bidirectional Mendelian Randomization Study
Authors' conclusion
Our study suggests that variations in normal-range thyroid function are causally associated with the diagnosis of MetS and with lipid profile, while in the reverse direction, HDL-C has a plausible causal effect on reference-range TSH levels.
Study context
- Population
- Genome-wide association studies (GWAS) summary statistics: Thyroid-stimulating hormone (TSH), FT4, metabolic syndrome (MetS), waist circumference, fasting blood glucose, hypertension, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C)GWAS summary statistics · TSH 119,715 · FT4 49,269 · MetS 291,107 · waist circumference 462,166 · fasting blood glucose 281,416 · hypertension 463,010 · TG 441,016 · HDL-C 403,943
- Comparison
- Genetically predicted thyroid function (TSH, FT4) vs MetS and its components, and vice versa
- Outcome
- MetS risk (main analysis: multiplicative random effects IVW)
Methodological detailssummary-level GWAS data, multiplicative random effects inverse variance weighted (IVW) main analysis, sensitivity analyses: weighted median, weighted mode, MR-Egger, CAUSE
- Summary-level GWAS data
- Multiplicative random effects IVW main analysis
- Sensitivity analyses: weighted median, weighted mode, MR-Egger, CAUSE
Main finding
As reported in the abstract
MetS risk per genetically predicted higher FT4
Higher FT4 lowers risk of MetS, OR
0.96
P = .037
Further findings
HDL-C per genetically predicted FT4
- Positive association, β
- 0.02 (P = .008)
- Consistent across Mendelian randomization (MR) analyses; confirmed with CAUSE
TG per genetically predicted TSH
- Positive association, β
- 0.01 (P = .044)
- Consistent across MR analyses; confirmed with CAUSE
Reverse direction: TSH per genetically predicted HDL-C
- Negative association, β
- −0.03 (P = .046)
- Main IVW analysis
Original publication
Thyroid Function and Metabolic Syndrome: A Two-Sample Bidirectional Mendelian Randomization Study. J Clin Endocrinol Metab. Published 20 June 2023. doi:10.
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