Date of Award

January 2026

Document Type

Open Access Thesis

Degree Name

Master of Public Health (MPH)

Department

School of Public Health

First Advisor

Zeyan Liew

Second Advisor

Andrew DeWan

Abstract

Cerebral palsy (CP) is a neuromotor disorder that is strongly associated with adverse perinatal conditions. Thyroid dysfunction in pregnancy was suggested to affect CP risk in a few cohort studies, but the evidence is not yet conclusive. We conducted a two-sample MR study to explore the effect of thyroid function on the risk of CP in offspring, and preterm birth as a potential mediator. Genetic instruments for hyperthyroidism and hypothyroidism were obtained from a large European genome-wide association study (GWAS) by Sakaue et al. (2021), instruments for free thyroxine (FT4) and thyrotropin (TSH) were derived from the ThyroidOmics Consortium, and the genetic data for CP were obtained from FinnGen. Genetic instruments for preterm birth, a potential mediator, was derived from the Early Growth Genetics Consortium. Primary analyses were performed using the inverse variance weighted method, with sensitivity tests using MR Egger, weighted median, and weighted mode approaches. Heterogeneity and horizontal pleiotropy were assessed using Cochran’s Q statistic and the MR Egger intercept. Genetically-predicted hyperthyroidism was associated with increased odds of CP (IVW OR=1.10, 95% CI 1.02–1.18; p=0.008). In contrast, no effect on CP estimated for hypothyroidism, FT4, or TSH levels. For the potential mediator, only higher FT4 levels but not other genetically predicted thyroid function markers evaluated were associated with preterm birth (OR=1.13, 95% CI 1.04–1.23; p=0.003). Genetic liability to hyperthyroidism may increase the risk of CP, but this association may not be mediated through preterm birth. Overall, our results suggest that thyroid-related traits may influence CP risk, but research data on genetic and maternal thyroid function during the critical time period of offspring development is needed to confirm our findings.

Comments

This is an Open Access Thesis.

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