Serum iron status and risk of Tourette's syndrome: a Mendelian randomization study

Tourette's syndrome (TS) is a common neurodevelopmental disorder with tics, emerging in childhood or adolescence and linked to neurotransmitter system abnormalities. Given iron's key role in neurotransmitter synthesis and transport, a close link between serum iron status and TS is hypothesized. But current studies, partly due to their inherent limitations, offer inconclusive evidence. A Mendelian randomization (MR) analysis was conducted. The analysis utilized summary statistics from two genome-wide association studies (GWAS) for TS (primary study: N = 456,348; and replication study: N = 21,081) and four GWASs related to serum iron status. The inverse variance-weighted MR method was used to evaluate the relationship between serum iron status and risk of TS using both the primary dataset and the replication dataset. Additionally, four other MR methods, which are more robust to pleiotropy and outliers, were used for sensitivity analyses. The analysis revealed no significant association between serum iron status and risk of TS (all Ps > 0.05). Repeated analysis with an independent TS sample yielded consistent results.

This MR study failed to uncover substantial evidence supporting a causal relationship between serum iron status in risk of TS due to its weak proxies to reflect brain iron levels. Therefore, additional validation from clinical and experimental investigations is warranted.

• A close link between serum iron status and Tourette's syndrome (TS) is hypothesized, because of iron's key role in neurotransmitter synthesis and transport. But current studies, partly due to their inherent limitations, offer inconclusive evidence.

• No substantial evidence supporting a causal relationship between serum iron status and risk of TS has been observed, even estimated by the Mendelian randomization design which can effectively control interfering factors such as the environment, heterogeneity, and reverse associations.