We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Mendelian Randomization Highlights the Causal Role of Normal Thyroid Function on Blood Lipid Profiles.
- Authors
Wang, Yanjun; Guo, Ping; Liu, Lu; Zhang, Yanan; Zeng, Ping; Yuan, Zhongshang
- Abstract
The association between thyroid function and dyslipidemia has been well documented in observational studies. However, observational studies are prone to confounding, making it difficult to conduct causal inference. We performed a 2-sample bidirectional Mendelian randomization (MR) using summary statistics from large-scale genome-wide association studies of thyroid stimulating hormone (TSH), free T4 (FT4), and blood lipids. We chose the inverse variance–weighted (IVW) method for the main analysis, and consolidated results through various sensitivity analyses involving 6 different MR methods under different model specifications. We further conducted genetic correlation analysis and colocalization analysis to deeply reflect the causality. The IVW method showed per 1 SD increase in normal TSH was significantly associated with a 0.048 SD increase in total cholesterol (TC; P < 0.001) and a 0.032 SD increase in low-density lipoprotein cholesterol (LDL; P = 0.021). A 1 SD increase in normal FT4 was significantly associated with a 0.056 SD decrease in TC (P = 0.014) and a 0.072 SD decrease in LDL (P = 0.009). Neither TSH nor FT4 showed causal associations with high-density lipoprotein cholesterol and triglycerides. No significant causal effect of blood lipids on normal TSH or FT4 can be detected. All results were largely consistent when using several alternative MR methods, and were reconfirmed by both genetic correlation analysis and colocalization analysis. Our study suggested that, even within reference range, higher TSH or lower FT4 are causally associated with increased TC and LDL, whereas no reverse causal association can be found.
- Subjects
BLOOD lipids; THYROID gland; THYROTROPIN; HIGH density lipoproteins; GENETIC correlations; CAUSAL inference
- Publication
Endocrinology, 2021, Vol 162, Issue 5, p1
- ISSN
0013-7227
- Publication type
Article
- DOI
10.1210/endocr/bqab037