Height, Autoimmune Thyroid Disease, and Thyroid Cancer: A Mendelian Randomization Study.

Area of Science:

• Genetics and Epidemiology
• Endocrinology
• Cancer Research

Background:

• Epidemiological studies suggest a correlation between increased height and elevated risks of hypothyroidism and thyroid cancer.
• The causal relationship between height and thyroid conditions, including autoimmune thyroid disease (AITD) and thyroid cancer, requires further investigation.
• AITD, a primary cause of hypothyroidism, makes it a relevant outcome for studying height-related thyroid associations.

Approach:

• Utilized Mendelian randomization (MR) analysis with genetic instruments for height derived from a large-scale genome-wide association meta-analysis (up to 5.4 million individuals).
• Collected summary-level data for AITD (30,234 cases) and thyroid cancer (3001 cases) from extensive genome-wide association studies.
• Performed bidirectional MR to assess potential reverse causation between AITD and adult height.

Key Points:

• A 1-standard deviation (SD) increase in genetically predicted height was associated with a 4% increased risk of AITD (95% CI: 1.02–1.07, p=1.99E-03).
• A 1-SD increase in genetically predicted height was associated with a 15% increased risk of thyroid cancer (95% CI: 1.07–1.23, p=2.32E-04).
• Bidirectional MR analyses found no evidence of a causal effect of AITD on adult height.

Conclusions:

• Genetically predicted height is causally associated with an increased risk of both AITD and thyroid cancer.
• No evidence suggests that AITD causally influences adult height.
• Findings highlight height-related pathways as potential targets for understanding the mechanisms underlying AITD and thyroid cancer.