TY - JOUR
T1 - Genome-wide DNA methylation meta-analysis in the brains of suicide completers
AU - Policicchio, Stefania
AU - Washer, Sam
AU - Viana, Joana
AU - Iatrou, Artemis
AU - Burrage, Joe
AU - Hannon, Eilis
AU - Turecki, Gustavo
AU - Kaminsky, Zachary
AU - Mill, Jonathan
AU - Dempster, Emma L.
AU - Murphy, Therese M.
N1 - Funding Information:
We are grateful to all the patients and control subjects who contributed to this study. The authors would like to acknowledge support of the Brain and Behaviour Research Foundation through a NARSAD Young Investigator Grant to T.M.M. and from the UK Medical Research Council (MRC) (grant number MR/ K013807/1) to J.M. Z.K. would like to acknowledge funding from the NIH grant (NIMH 1R21MH094771). The Douglas Bell Canada Brain Bank is supported by the FRQS through the Quebec Network on Suicide, Mood Disorders and Related Disorders, and by Brain Canada through an infrastructure grant. E.L.D. would like to acknowledge the AMS Springboard scheme that supported SW studentship.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Suicide is the second leading cause of death globally among young people representing a significant global health burden. Although the molecular correlates of suicide remains poorly understood, it has been hypothesised that epigenomic processes may play a role. The objective of this study was to identify suicide-associated DNA methylation changes in the human brain by utilising previously published and unpublished methylomic datasets. We analysed prefrontal cortex (PFC, n = 211) and cerebellum (CER, n = 114) DNA methylation profiles from suicide completers and non-psychiatric, sudden-death controls, meta-analysing data from independent cohorts for each brain region separately. We report evidence for altered DNA methylation at several genetic loci in suicide cases compared to controls in both brain regions with suicide-associated differentially methylated positions enriched among functional pathways relevant to psychiatric phenotypes and suicidality, including nervous system development (PFC) and regulation of long-term synaptic depression (CER). In addition, we examined the functional consequences of variable DNA methylation within a PFC suicide-associated differentially methylated region (PSORS1C3 DMR) using a dual luciferase assay and examined expression of nearby genes. DNA methylation within this region was associated with decreased expression of firefly luciferase but was not associated with expression of nearby genes, PSORS1C3 and POU5F1. Our data suggest that suicide is associated with DNA methylation, offering novel insights into the molecular pathology associated with suicidality.
AB - Suicide is the second leading cause of death globally among young people representing a significant global health burden. Although the molecular correlates of suicide remains poorly understood, it has been hypothesised that epigenomic processes may play a role. The objective of this study was to identify suicide-associated DNA methylation changes in the human brain by utilising previously published and unpublished methylomic datasets. We analysed prefrontal cortex (PFC, n = 211) and cerebellum (CER, n = 114) DNA methylation profiles from suicide completers and non-psychiatric, sudden-death controls, meta-analysing data from independent cohorts for each brain region separately. We report evidence for altered DNA methylation at several genetic loci in suicide cases compared to controls in both brain regions with suicide-associated differentially methylated positions enriched among functional pathways relevant to psychiatric phenotypes and suicidality, including nervous system development (PFC) and regulation of long-term synaptic depression (CER). In addition, we examined the functional consequences of variable DNA methylation within a PFC suicide-associated differentially methylated region (PSORS1C3 DMR) using a dual luciferase assay and examined expression of nearby genes. DNA methylation within this region was associated with decreased expression of firefly luciferase but was not associated with expression of nearby genes, PSORS1C3 and POU5F1. Our data suggest that suicide is associated with DNA methylation, offering novel insights into the molecular pathology associated with suicidality.
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U2 - 10.1038/s41398-020-0752-7
DO - 10.1038/s41398-020-0752-7
M3 - Article
C2 - 32075955
AN - SCOPUS:85079735400
SN - 2158-3188
VL - 10
JO - Translational psychiatry
JF - Translational psychiatry
IS - 1
M1 - 69
ER -