An Exploratory Study of the Association Between the UGT1A1*28 Polymorphism and Polygenic Risk for Hypertrophic Cardiomyopathy: Evidence for Overdominance in an Unrelated European Cohort

Version 2 represents a complete shift in the study's focus due to an honest methodological mistake in the original draft. While running the automated pipeline for Version 1, I accidentally pulled the wrong Polygenic Score (PGS) model. Instead of the intended cognitive model, the script used a model for Hypertrophic Cardiomyopathy (HCM; model ID: PGS004911). Fortunately, the underlying extraction of the UGT1A1 gene and all statistical calculations were mathematically sound. This means the significant correlation I observed (p=0.0064) was actually a real link between the UGT1A1 variant and polygenic risk for HCM. Given that mildly elevated bilirubin (Gilbert's Syndrome) is widely known for its cardioprotective and antioxidative benefits, this accidental discovery actually makes a lot of biological sense. As a result, I have entirely rewritten the manuscript. Version 2 leaves neurocognition behind and explores a new, cardiovascular hypothesis: that the UGT1A1 polymorphism might act as a natural compensatory buffer (heterozygote advantage) for people with higher genetic risk for heart issues.