Statistical genetic association analysis of gestational diabetes in a population with high levels of consanguineous marriage

The population of Bradford is of particular interest from a statistical genetics perspective due to a combination of it being highly stratified and showing high levels of consanguineous unions. Consanguineous marriages are thought to cause an increased risk of both common and rare recessive genetic disorders. One subgroup in the study has high rates of more common disorders, such as gestational diabetes, and the increased risk of these may reflect genetic predisposition resulting from common, low penetrance, genetic variants. This study will focus on gestational diabetes as it has great implications on mothers and their offspring, not to mention affecting disproportionately various ethnic groups.
Common, low-penetrance genetic variants are typically identified by genome-wide association studies of several thousand individuals genotyped at hundreds of thousands of loci. However, standard genetic analyses assume that the populations that are being studied consist of unrelated, randomly-mating, outbred individuals. We will show that all three of these conditions are likely to be violated here, which is to be expected given the tendency for marriage to occur within biraderis and between close relatives.
Thus, in order for this genome-wide association study to report accurate findings, we first need to understand and account for the population structure and marriage patterns in the population to enable us to analyse the data correctly. In order to do this, we will make use of the self-reported answers and build upon them by using genotype data from the Born in Bradford cohort study.
Finally, the genetic determinants of GDM that are found will be compared to other published studies.