Approved Research
Parity effects on sex differences in the human immune system
Lay summary
Sex differences exist across a wide range of human diseases, yet they are understudied and are not easily explained by reproductive hormones, environmental exposures, or increases in surveillance alone. The "Pregnancy Compensation Hypothesis" (PCH) posits that sex differences in the immune system reflect an adaptation to selection on female immunity during pregnancy, during which increased immunomodulation is required to reduce immune responses to the fetus while maintaining the ability to respond to pathogens. In humans, fewer pathogens and lower numbers of pregnancy in urban environments is expected to leave female immune systems under-stimulated, creating an "evolutionary mismatch" which exacerbates sex differences in immunity and female autoimmune disease risk. Yet, robust tests of this mismatch hypothesis are rare.
To begin addressing how lifestyle changes impact immune system sex differences, we have previously conducted a direct test for sex differences in immune system biomarkers within a single population living in both traditional and urban environments, as well as testing for generalizable trends across multiple populations. While interesting, our approaches so far do not directly test the effects of parity on autoimmune disease risk or cancers. The breadth and depth of the UK Biobank will give us the power to conduct this analysis within a single urban cohort.
The first aim of this project is to use the UK Biobank data to identify disease occurrence and the sex ratio of a wide range of cancers and autoimmune diseases. We then aim to directly test whether number of pregnancies predicts autoimmune diseases later in life for females. This research will give insight into the complicated relationship between lifestyle changes and disease risk. Specifically, we will gain a better understanding of how autoimmune diseases can be explained by parity (which is often lower in post-industrial societies due to greater access to family planning resources) and test hypotheses regarding the diversity of autoimmune diseases and cancers, both of which have broad biomedical implications and public interest.