Project ID NS-MH2024_63

ThemeNS-MH

Co Supervisor 1A Institute of Psychiatry, Psychology & Neuroscience, School of Mental Health & Psychological Sciences, Social, Genetic & Developmental Psychiatry CentreWebsite

Co Supervisor 1B Institute of Psychiatry, Psychology & Neuroscience, School of Mental Health & Psychological Sciences, Department of Biostatistics & Health InformaticsWebsite

Dissecting the Epigenetic Basis of Eating Disorders using Nanopore sequencing data

Eating disorders (ED) affect ~8% of the global population and they are often chronic and cause substantial costs. ED are complex with both genetic and environmental causes. Epigenetics, biological mechanisms that underlie the interaction between genes and the environment, might play significant roles in the aetiology and manifestation of ED, are currently understudied. To address this research gap, we propose to study the epigenetic basis of ED using nanopore DNA methylation sequencing data in 4,000 participants from the Eating Disorders Genetics Initiative United Kingdom UK dataset (EDGI UK; edgiuk.org).

The overarching aim of this project is to identify differential epigenetic, i.e. DNA methylation, signatures associated with different types of Eating Disorders and related phenotypes using next-generation Nanopore epigenetic sequencing data from 4000 individuals.

The PhD student will have the unique opportunity working on one of the largest epigenetics sequencing datasets within psychiatry; relevant data analyses training will be provided by supervisors’ teams. The student will also have the opportunity to work with ED charities and Lived Experience, coproducing the research wherever possible, as part of ongoing participant and public engagement for EDGI UK research.

Year 1: Perform background reading and write a literature review on “Epigenetics in Eating Disorders”. Undertake relevant data analytic trainings and perform data QC and processing on Nanopore DNA methylation sequencing data.?Year 2: Conduct epigenome-wide association study (EWAS) to detect epigenetic signatures of eating disorder diagnoses (Objective 2). Year 3: Conduct epigenome-wide association study (EWAS) to detect epigenetic signatures of extreme BMI phenotypes and lifetime minimum and maximum BMI, as well as other extreme behaviours such as purging. Perform sensitivity analyses using single diagnostic groups of no other eating disorders/BMI-related comorbidities. Year 4: Complete analyses and writing up of papers and thesis.

Representative Publications

Alameda, L., Liu, Z., Sham, P., … Murray, R, Wong, C. (2023). Exploring the mediation of DNA methylation across the epigenome between childhood adversity and First Episode of Psychosis—findings from the EU-GEI study. Molecular Psychiatry. https://doi.org/10.1038/s41380-023-02044-9

Alameda, L., Trotta, G., Quigley, H., Rodriguez, V., Gadelrab, R., Dwir, D., Dempster, E., Wong, C. C. Y.*, & Forti, M. D.* (2022). *Joint senior authorships; Can epigenetics shine a light on the biological pathways underlying major mental disorders? Psychological Medicine, 52(9), 1645-1665. https://doi.org/10.1017/S0033291721005559

Hu, J., et al., Iacoangeli, A. (2021). DGLinker: flexible knowledge-graph prediction of disease–gene associations. Nucleic acids research, https://doi.org/10.1093/nar/gkab449

Iacoangeli, A, et al. “SCFD1 expression quantitative trait loci in amyotrophic lateral sclerosis are differentially expressed.” Brain communications 3.4 (2021) https://doi.org/10.1093/braincomms/fcab236

Marriott, H., et al., & Iacoangeli, A. (2023). DNAscan2: a versatile, scalable, and user-friendly analysis pipeline for human next-generation sequencing data. Bioinformatics, https://doi.org/10.1093/bioinformatics/btad152