Hilary started her university studies in Australia and then completed her PhD with Peter Donnelly at the Wellcome Trust Centre for Human Genetics in Oxford in 2015. There, she worked on an eclectic set of projects ranging from rare disease genomics to population genetics of the platypus. She moved to the Sanger Institute initially as a postdoc with Jeff Barrett, and then started her own group there in 2018. Her group analyses large-scale genetic and electronic health record data to explore the genetic architecture of neurodevelopmental disorders and traits, as well as complex diseases in populations with high levels of parental relatedness (consanguinity).

Insights into the genetics of neurodevelopmental conditions and traits from large British cohorts

I will present results from two projects focused on cognitive ability in population-based cohorts with relevance for rare neurodevelopmental conditions (NDCs). In the first, we examine the impact of common and rare variants associated with NDCs on cognitive ability measured longitudinally throughout childhood in British birth cohorts. We find evidence for time-varying effects which differ between common and rare variants, and which vary across the phenotype distribution. Our results suggest a possible explanation for the incomplete penetrance of rare damaging variants in families with NDCs. In the second project, we impute missing values for verbal-numerical reasoning (fluid intelligence) in UK Biobank, increasing the sample size from ~284k to ~455k, and use this larger sample to increase power for genetic analyses. Through this, we identify 26 genes in which rare damaging variants are associated with fluid intelligence at FDR<1%, of which 14 are known NDC genes. Our results suggest that this may be a fruitful strategy to increase power for identifying new NDC genes in patient cohorts.