4-year PhD Studentship: How does parental education increase risk to ADHD in the offspring? at University of Bristol on FindAPhD.com

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Dr E Stergiakouli, Dr L Howe No more applications being accepted Self-Funded PhD Students Only

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Bristol United Kingdom Epidemiology Genetics

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). However, the mechanisms linking parental education with ADHD are uncertain. Disentangling the individual effects of potential mechanisms, whilst accounting for genetic and environmental confounding is required.

Aims and objectives

In this project, we will explore potential mechanisms linking educational attainment with ADHD, using cutting-edge genetically-informed methods to assist with causal inference.

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’s 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.

Keywords

ADHD, neurodevelopmental disorders, genetics, epidemiology, Mendelian randomization

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.

Please visit the Faculty of Health Sciences website for details of how to apply

Funding Notes

This project is open for University of Bristol PGR scholarship applications (closing date 25th February 2022)
The University of Bristol PGR scholarship pays tuition fees and a maintenance stipend (at the minimum UKRI rate) for the duration of a PhD (typically three years but can be up to four years).

References

1. Thapar A, Cooper M. Attention deficit hyperactivity disorder. Lancet. 2016; 387(10024):1240-50.
2. Leppert B et al. Association of Maternal Neurodevelopmental Risk Alleles With Early-Life Exposures. JAMA Psychiatry. 2019;76(8):834–842.
3. Dardani et al. Is genetic liability to ADHD and ASD causally linked to educational attainment?, Int. J. Epidemiol. 2021; doi.org/10.1093/ije/dyab107
4. Weiner D et al. Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders. Nat Genet 49, 978–985 (2017).
5. Brumpton, B et al. Avoiding dynastic, assortative mating, and population stratification biases in Mendelian randomization through within-family analyses. Nat Commun 2020 11, 3519.
6. Sanderson E et al. An examination of multivariable Mendelian randomization in the single-sample and two-sample summary data settings. Int J Epidemiol. 2019;48(3):713-727.