B4196 - Epigenetic pathways to youth self-injurious thoughts and behaviours dissecting phenotypic heterogeneity and time course - 23/11/2022

B number: 
Principal applicant name: 
Gabriel Fries | University of Texas Health Science Center at Houston (USA)
Salahudeen Mirza, Becky Mars, Sarah Watkins
Title of project: 
Epigenetic pathways to youth self-injurious thoughts and behaviours: dissecting phenotypic heterogeneity and time course
Proposal summary: 

Suicide is a leading cause of death among youth, but little is known about the associated risk factors. Growing recognition that the existing clinical and psychological measures do not predict suicidal behaviour very strongly has contributed to a focus on the genetic correlates and predictors of suicide risk. Although genotypes do not change across the lifespan, an epigenetic process known as DNA methylation is responsive to environmental experience and can modify the expression of certain genes. Although numerous investigations have cross-sectionally identified a role for DNA methylation changes in self-injurious thoughts and behaviours (such as suicide attempt, suicidal thoughts, and self-injury without suicidal intent), these studies have largely focused on adults. Given that development is associated with numerous biological, epigenetic, and psychosocial changes, there is a need to better identify specific DNA methylation risk factors in youth, rather than extrapolating from work in adults. In this project, we aim to conduct epigenome-wide association studies (case-control comparison of methylation at numerous locations in the genome) of suicide ideation; suicide attempt history; and self-injury without suicidal intent; in teenagers who are part of the Avon Longitudinal Study of Parents and Children. We will also be able to make use of methylation measurements taken in childhood and at birth to trace any methylation differences backward, in an attempt to understand when they might emerge. These findings will be essential to identifying youth-specific risk factors for suicide, and ultimately contribute to efforts to better inform risk assessment as well as biologically informed interventions.

Impact of research: 
This project will kickstart future projects investigating the biological underpinnings of youth SITBs. This will be the first epigenome wide association study of teenage suicide attempt, suicidal thoughts, or non suicidal self harm, and the first to employ longitudinal analyses using childhood or perinatal methylation. Further studies of functional genomics and longitudinal designs, including person-centered analyses, will be able to build on these foundational findings. Additionally, replication efforts in other cohorts will be welcome additions to the growing body of research in youth suicide biology. We anticipate that this will be a very well-received body of work.
Date proposal received: 
Wednesday, 9 November, 2022
Date proposal approved: 
Monday, 21 November, 2022
Genetic epidemiology (including association studies and mendelian randomisation), Mental health, Methylation wide association study, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Birth outcomes, Childhood - childcare, childhood adversity, Development, Epigenetics, Genetic epidemiology, Genetics, Genomics, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc.