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All analysis code and supplementary information is publicly available on OSF 🤓 osf.io/k46gu/

These findings advance our understanding of the genetic architecture of hypothalamic subunits related to oxytocin and vasotocin and selected psychiatric/metabolic traits. We provide new avenues for future research and help decipher oxytocinergic-vasotocinergic hypothalamic systems in well-being.

The genes associated with these loci were enriched in neuroimaging, neurodegeneration and different metabolic markers. They were further found to be up-regulated in tissues such as blood vessel or down-regulated in the liver.

Subsequently, we pinpointed 95 unique loci across all subunits and traits. Most were identified for the psychiatric/metabolic traits in combination with the tubular-superior subunit, followed by the anterior-superior (displayed in the Manhattan plot), and lastly the anterior-inferior subunit.

We show that the three subunits (anterior-inferior, anterior-superior, tubular-superior) share stronger overlap with psychiatric/neurodevelopmental (autism, schizophrenia, bipolar disorder) than with metabolic (e.g., bone mineral density, BMI, HDL, LDL, systolic blood pressure) traits.

We deployed bivariate mixture models and conjunctional FDR to estimate the global and local genetic overlap between the three oxytocinergic-vasotocinergic hypothalamus subunits and ten psychiatric and metabolic traits related to oxytocin and vasotocin signaling.

Oxytocin and vasotocin are produced in the supraoptic and paraventricular nuclei within three hypothalamic subunits. The neuropeptides appear to contribute to co-occurring metabolic and psychiatric traits. The genetic pathways between these hypothalamic volumes and traits remain unknown.