Continue with FacebookLooking to list your PhD opportunities? Log in here.
About the Project
Background
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.
Apply for this project
This project will be based in Bristol Medical School - Population Health Sciences.
Please contact brms-pgradmin@bristol.ac.uk for further details on how to apply.
References
Thapar A, Cooper M. Attention deficit hyperactivity disorder. Lancet. 2016 Mar 19;387(10024):1240-50. doi: 10.1016/S0140-6736(15)00238-X.
Leppert B et al. Association of Maternal Neurodevelopmental Risk Alleles With Early-Life Exposures. JAMA Psychiatry. 2019;76(8):834–842. doi:10.1001/jamapsychiatry.2019.0774
Dardani et al. Is genetic liability to ADHD and ASD causally linked to educational attainment?, Int. J. Epidemiol. 2021;, dyab107, https://doi.org/10.1093/ije/dyab107
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). https://doi.org/10.1038/ng.3863
Brumpton, B et al. Avoiding dynastic, assortative mating, and population stratification biases in Mendelian randomization through within-family analyses. Nat Commun 11, 3519 (2020). https://doi.org/10.1038/s41467-020-17117-4
Sanderson E et al. An examination of multivariable Mendelian randomization in the single-sample and two-sample summary data settings. Int J Epidemiol. 2019 Jun 1;48(3):713-727. doi: 10.1093/ije/dyy262.
Leppert B et al. Association of Maternal Neurodevelopmental Risk Alleles With Early-Life Exposures. JAMA Psychiatry. 2019;76(8):834–842. doi:10.1001/jamapsychiatry.2019.0774
Dardani et al. Is genetic liability to ADHD and ASD causally linked to educational attainment?, Int. J. Epidemiol. 2021;, dyab107, https://doi.org/10.1093/ije/dyab107
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). https://doi.org/10.1038/ng.3863
Brumpton, B et al. Avoiding dynastic, assortative mating, and population stratification biases in Mendelian randomization through within-family analyses. Nat Commun 11, 3519 (2020). https://doi.org/10.1038/s41467-020-17117-4
Sanderson E et al. An examination of multivariable Mendelian randomization in the single-sample and two-sample summary data settings. Int J Epidemiol. 2019 Jun 1;48(3):713-727. doi: 10.1093/ije/dyy262.
Email Now
You haven’t included a message. Providing a specific message means universities will take your enquiry more seriously and helps them provide the information you need.
Why not add a message here
Why not add a message here
* required field
The information you submit to University of Bristol will only be used by them or their data partners to deal with your enquiry, according to their privacy notice. For more information on how we use and store your data, please read our privacy statement.
Search suggestions
Based on your current searches we recommend the following search filters.
Check out our other PhDs in Bristol, United Kingdom
Check out our other PhDs in United Kingdom
Start a New search with our database of over 4,000 PhDs
PhD suggestions
Based on your current search criteria we thought you might be interested in these.
Belongingness in Health Professions Education: What does it mean and how is it experienced by distance learners?
University of Dundee
The transgenerational dimension of senescence: How do parental age and environment affect offspring development and fitness?
UNSW Sydney
Belongingness in Faculty: What does it mean and how is it experienced by sessional tutors?
University of Dundee