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Dr Evie Stergiakouli,
Dr Laura Howe, Dr Rachel Blakey, Ms Christina Dardani
Applications accepted all year round
Self-Funded PhD Students Only
Bristol
United Kingdom
Child Psychology
Developmental Psychology
Genetics
Health Psychology
Human Genetics
Neurology
Neuropsychology
Neuroscience
Biological Sciences
Psychology
About the Project
Rationale
Neurodevelopmental and mental health problems in childhood have been linked to adverse physical health outcomes in both childhood and adult life. For example, genetic risk scores for ADHD have been associated with adverse lifestyle and physical health outcomes even in individuals from the general population who do not necessarily exhibit the disorder (1). Causal analyses have linked ADHD to childhood obesity and coronary artery disease (2). However, neurodevelopmental disorders and more specifically ADHD are also associated with adverse socioeconomic factors and impaired educational attainment (3).
Aims & Objectives
In this project, we aim to investigate the effect of neurodevelopmental and mental health problems in childhood on child and adult physical health while taking into account the strong associations of neurodevelopmental problems and mental health with socioeconomic factors, education and parental psychopathology.
Methods
We will construct polygenic risk scores for childhood neurodevelopmental and mental health conditions in parents and children from the general population to investigate their associations with adult physical health and perform Polygenic Transmission Disequilibrium test (4) to asses genetic risk transmitted from parents to children. We will perform Multivariable Mendelian randomization (5) to disentangle the effects of genetic liability to neurodevelopmental problems on physical health accounting for socioeconomic factors. We will apply sensitivity analyses including weighted median, weighted mode, MR-Egger regression, MR-PRESSO and colocalization analyses as well as other causally informative designs to assess and adjust for pleiotropy. There is also the opportunity to contribute to large-scale meta-analyses including the Norwegian Mother, Father and Child Cohort Study (MoBa) and initiate collaborations with external researchers.
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.
If you have secured your own sponsorship or can self-fund this PhD please visit our information page here for further information on the department of Population Health Science and how to apply.
References
1) Leppert 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
2) Leppert et al. The Effect of Attention Deficit/Hyperactivity Disorder on Physical Health Outcomes: A 2-Sample Mendelian Randomization Study, AJE 2021; 190 (6), 1047–1055, https://doi.org/10.1093/aje/kwaa273
3) Dardani et al. Is genetic liability to ADHD and ASD causally linked to educational attainment?, IJE 2021;, dyab107, https://doi.org/10.1093/ije/dyab107
4) Weiner et al. Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders. Nat. Genet. 2017 49, 978
5) Sanderson et al. An examination of multivariable Mendelian randomization in the single-sample and two-sample summary data settings. IJE 2018; 1;48(3):713-727. doi: 10.1093/ije/dyy262.
2) Leppert et al. The Effect of Attention Deficit/Hyperactivity Disorder on Physical Health Outcomes: A 2-Sample Mendelian Randomization Study, AJE 2021; 190 (6), 1047–1055, https://doi.org/10.1093/aje/kwaa273
3) Dardani et al. Is genetic liability to ADHD and ASD causally linked to educational attainment?, IJE 2021;, dyab107, https://doi.org/10.1093/ije/dyab107
4) Weiner et al. Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders. Nat. Genet. 2017 49, 978
5) Sanderson et al. An examination of multivariable Mendelian randomization in the single-sample and two-sample summary data settings. IJE 2018; 1;48(3):713-727. doi: 10.1093/ije/dyy262.
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