To validate our findings, we investigated the phenome-wide spectrum associated with this locus and the regulatory effect of rs8052287 (i.e., the index variant) on the tissue-specific transcriptomic profile of the genes located in this region. Gene-based and single-variant phenome-wide scans showed a similar pattern of associations related to physical health and characteristics. These included hypothyroidism, anthropometric traits, male hair loss, and hematological parameters. These phenotypic associations can be linked to altered thyroid function43. Tissue-specific transcriptomic analysis confirmed that rs8052287 actively regulates multiple genes in thyroid tissues. Due to the high gene density in the locus identified (rs8052287 regulates the transcriptomic profile of 26 genes), it is hard to pinpoint the gene(s) responsible for the interaction with polysubstance dependence. However, the evidence leading to altered thyroid function supports an intriguing hypothesis. Previous studies highlighted the potential role of thyroid dysfunction in suicide risk, especially among psychiatric patients44. This is in line with the known effect of altered thyroid function on mental health43. In a recent genome-wide analysis, we observed that hypothyroidism is genetically correlated with several behavioral traits including fatigue, anxiety,
