Quantifying the effect of different levels of consanguinity and biraderi membership on risk of congenital anomaly

It has previously been shown (Sheridan et al, 2013) using self-reported consanguinity in the Born in Bradford cohort that the risk of congenital anomalies is increased in the children of parents who are first cousins. However, this risk appears to be greater in Bradford Pakistanis than in the rest of the UK and consanguinity only accounts for a relatively small portion of the overall risk. We suspect that this is because, as we have previously demonstrated, self-reported consanguinity does not fully capture relatedness between parents due to many generations of consanguineous marriage (Arciero et al, 2021). As a result of this the risk to a child of first cousins appears to be higher in Bradford Pakistanis, because they are in fact genetically more closely related than first cousins. Similarly the proportion of the risk due to consanguineous marriage is underestimated because much of the consanguinity is not accounted for in self-reporting. Thus we would like to repeat this analysis using genetically-inferred consanguinity.

We have already demonstrated from the genotype data that biraderi can, with reasonable accuracy, be estimated from the genotype data. At the same time we have shown that the coefficient of inbreeding is correlated with self-reported consanguinity.

We would like to combine our estimates with the data that have been collected on congenital disorders, including those occurring after the age of 1 (Bishop et al 2017). We will then estimate the contribution of consanguinity to risk of such disorders and include both reported biraderi and estimated biraderi to judge whether either membership of a particular biraderi or intra-biraderi marriage increase risk of a congenital disorder. We will further compare the effects of these on subtypes of congenital disorder, including comparing those with onset (or at least recognition) at age<1 against those with onset at age >1. We will further investigate whether consanguinity additionally impacts on educational attainment by using SATS results at age 7.

I would like (in addition to data I already have, such as genotype data): Congenital anomaly data (including whatever categorisation of these is available and age of onset/diagnosis)
Markers of socioeconomic status (including educational attainment, income, etc.)
Smoking/alcohol consumption
SATS results of children at age 7 (as a marker of educational attainment)

This was previously approved in 2018 as SP283 as a PhD project though we never reached the analytical stage. I am reapplying now for an MSc project.