Polygenic risk score analysis suggests hypothyroidism as a risk factor for Alzheimer’s disease

We found significant association between AD-PRS and nine conditions, with the most significant hypothyroidism and acquired hypothyroidism (adj-p < 1.3^-06). The AD-PRS was significantly lower in participants with these conditions. Additionally, an investigation into 355 measurement variables revealed a significant association for eighteen variables, with height and blood pressure showing a positive correlation with AD-PRS. Thyrotropin level (TSH) exhibited a negative correlation, aligning with hypothyroidism's association with lower PRS. This association remained significant even after accounting for hypothyroidism medications in the analysis, and was further confirmed in a replication study using the UK Biobank data (n = 390,543; p = 1.3^-23) CONCLUSION: Our results seem to demonstrate that the absence of HPT might be a factor enhancing AD resilience since it can balance the genetic risk factors, as non-affected individuals exhibited a significantly higher AD-PRS than HPT-affected individuals.