In this project we will be investigating whether a range of circulating factors within pregnant women have a causative role in influencing the birth weight of their babies.
Both low and high birth weights are key risk factors for disease and death rates of infants soon after they are born. Lower birth weight in the general population is also associated with an increased risk of a range of chronic diseases in adulthood, including cardiovascular disease, high blood pressure and type 2 diabetes.
We aim to adopt a genetic approach known as Mendelian randomization to investigate the role several factors could have on low birth weight. Mendelian randomization uses the principle that the random assortment of genotypes in meiosis (the process of cell division that produces sperm and eggs) is not influenced by the environment. Initially we are investigating whether the maternal rs1051730 variant in the CHRNA3 gene, which predisposes to greater smoking quantity, is associated with offspring birth weight.
As most common gene variants that are robustly associated with disease have small effects, very large numbers of individuals are often required to provide sufficient power to examine their roles. Therefore, investigating the association between birth weight and the rs1051730 variant requires collaboration with many groups to obtain data from numerous studies. We are carrying out a meta-analysis of data from >20,000 individuals. It is anticipated that these results will be completed by April 2012.
We are also starting to investigate whether maternal fasting glucose, triglyceride levels, blood pressure, caffeine levels, vitamin levels and other metabolites play a causative role in birth weight of the offspring.
In the future these genetic techniques will be employed to investigate causative relationships between a range of environmental factors and chronic human diseases.
This work is in collaboration with Prof Tim Frayling and Dr Rachel Freathy from the Complex Traits Genetics group at Peninsula Medical School.