The oxytocin signalling gene pathway contributes to the association between loneliness and cardiometabolic health.

Increasing evidence has shown adverse effects of loneliness on cardiometabolic health. The neuromodulator and hormone oxytocin has traditionally been linked with social cognition and behaviour. However, recent implications of the oxytocin system in energy metabolism and the overrepresentation of metabolic issues in psychiatric illness suggests that oxytocin may represent a mechanism bridging mental and somatic traits. To clarify the role of the oxytocin signalling system in the link between cardiometabolic risk factors and loneliness, we calculated the contribution of single nucleotide polymorphisms (SNPs) in the oxytocin signalling pathway gene-set (154 genes) to the polygenic architecture of loneliness and body mass index (BMI). We investigated the associations of these oxytocin signalling pathway polygenic scores with body composition measured using body magnetic resonance imaging (MRI), bone mineral density (BMD), haematological markers, and blood pressure in a sample of just under half a million adults from the UK Biobank (BMD subsample n = 274,457; body MRI subsample n = 9796). Our analysis revealed significant associations of the oxytocin signalling pathway polygenic score for BMI with abdominal subcutaneous fat tissue, HDL cholesterol, lipoprotein(a), triglycerides, and BMD. We also found an association between the oxytocin signalling pathway polygenic score for loneliness and apolipoprotein A1, the major protein component of HDL. Altogether, these results provide additional evidence for the oxytocin signalling pathway's role in energy metabolism, lipid homoeostasis, and bone density, and support oxytocin's complex pleiotropic effects.