Approved Research

Phenome-wide association study of genetic variants influencing lactation

Lay summary

Aim: To identify the range of biological and clinical traits associated with variations in genes influencing breast milk production. Lactation hormones such as prolactin and oxytocin are linked with diseases such as infertility and autism, and this study aims to identify novel diseases associated with these hormones.

Scientific rationale: Hormones stimulating breast milk production such as prolactin and oxytocin are essential for women's health and reproduction. Prolactin levels in the blood increase during pregnancy and lactation to promote breast development and milk synthesis, respectively. Oxytocin stimulates milk let-down during lactation. Therefore, appropriate control of these two hormones is required for breastfeeding, which in turn is associated with beneficial health outcomes for the mother such as reduced risk of diabetes, obesity, endometriosis, and breast and ovarian cancer. However it is unclear if prolactin and oxytocin affect the risk of these diseases in women. In addition, the influence of prolactin and oxytocin on men's health has not been assessed. Genetic alterations, such as mutations can lead to abnormal levels of these hormones in the blood, which is linked with adverse health outcomes. For example, low levels of oxytocin are associated with autistic spectrum disorders and high prolactin levels can cause infertility and lactation disorders. Prolactin and oxytocin are also important for other processes in the body such as regulation of blood sugar, bone health and social behaviours. However, the full range of biological functions and diseases influenced by prolactin and oxytocin remains unknown. This can be revealed by identifying genetic variations affecting prolactin and oxytocin, and understanding how these correlate with traits and disease outcomes in a given population. To address this, we will determine the association between genetic variations influencing lactation and the entire set of traits and diseases in UK Biobank participants, using an approach called phenome-wide association study.  

Project duration: 36 months

Public health impact: This study will provide insight into the range of biological processes and diseases which are influenced by lactation hormones such as prolactin and oxytocin. This has important implication for women's health, given the key roles of these hormones in reproduction and lactation. Findings from this study will also unravel novel gene-disease associations which will allow for personalised and improved therapy, and to also identify how drug therapies modulating lactation hormones may benefit patients with other conditions.