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  Investigating causal mechanisms between parental social disadvantage and risk of ADHD to the offspring


   Bristol Medical School

   Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Attention Deficit Hyperactivity Disorder (ADHD) is a chronic neurodevelopmental condition, characterised by persistent difficulties in the areas of attention span/impulse control. Approximately 65% of children diagnosed with ADHD have symptoms and impairment that persist into adulthood and ADHD can lead to educational, social, and occupational difficulties (1).

We have previously shown that higher genetic risk for ADHD is associated with younger maternal age at birth, lower educational attainment and other indicators of social disadvantage in mothers from the general population (2). Using Mendelian randomization (MR) we have also found evidence of higher genetic liability to ADHD causing lower educational attainment, and evidence of genetic liability to lower educational attainment increasing risk to ADHD independent of cognitive ability (3). Since ADHD manifests at a very young age, the causal effects of genetic liability to education on ADHD are likely to indicate parental effects. The causal link between parental education and ADHD could be mediated by optimal lifestyle and general health factors during pregnancy and/or socioeconomic factors linked to better access to educational resources. Disentangling the individual effects of each factor as well as assessing for genetic confounding is required.

Aims and objectives

In this project, we will explore the links between educational attainment, reproductive outcomes (age at first birth, number of live births), prenatal factors, socioeconomic status and other indicators of social disadvantage on ADHD.

Our aims are: 1. To assess the contribution of parental educational attainment on trajectories of ADHD traits in offspring and 2. To disentangle it from the offspring own genetic background and investigate the causal pathways linking parental educational attainment and offspring ADHD.

Methodology

This is an exciting opportunity for a student to perform advanced genetic epidemiological analyses on large multigenerational longitudinal cohorts from two countries: the Avon Longitudinal Study of Parents and Children in the UK and the Norwegian Mother and Child Cohort Study (MoBa) in Norway.

For aim 1, we will compare the associations of maternal and paternal genetic liability of educational attainment on ADHD trajectories from two general population samples with very different educational systems and social structures. Polygenic Transmission Disequilibrium tests will be used to assess if genetic liability to lower educational attainment is overtransmitted to offspring with ADHD (4).

For aim 2, we will use within-families MR (5) in MoBa to investigate causal effects of the offspring’s own genetic liability to education attainment while adjusting for parental genetic liability. We will also perform Multivariable Mendelian randomization (6) to account for multiple exposures (educational attainment, reproductive outcomes, prenatal factors, socioeconomic status) simultaneously. Finally, we will apply sensitivity analyses including weighted median, weighted mode, MR-Egger regression, MR-PRESSO and colocalization analyses to assess and adjust for pleiotropy.

Supervisors: Dr Evie Stergiakouli (primary supervisor), Dr Rachel Blakey, Prof Laura Howe, Dr Alex Havdhal (external based in Norway)

How to apply for this project

This project will be based in Bristol Medical School - Population Health Sciences in the Faculty of Health Sciences at the University of Bristol. Use this information to search for the relevant programme in our online application system.


Medicine (26) Nursing & Health (27)

References

1. Thapar A, Cooper M. Lancet. 2016 Mar 19;387(10024):1240-50. doi: 10.1016/S0140-6736(15)00238-X.
2. Leppert B et al. JAMA Psychiatry. 2019;76(8):834–842. doi:10.1001/jamapsychiatry.2019.0774
3. Dardani et al. Int. J. Epidemiol. 2021;, dyab107, https://doi.org/10.1093/ije/dyab107
4. Weiner D et al. Nat Genet 49, 978–985 (2017). https://doi.org/10.1038/ng.3863
5. Brumpton, B et al. Nat Commun 11, 3519 (2020). https://doi.org/10.1038/s41467-020-17117-4
6. Sanderson E et al. Int J Epidemiol. 2019 Jun 1;48(3):713-727. doi: 10.1093/ije/dyy262.

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