Individuals with 22q11.2 deletion have an increased risk of mental illness, with a large variation in the development and progression of ADHD, depression and schizophrenia. We investigated whether neonatal DNA methylation signatures in individuals with 22q11.2 deletion associate with mental illness later in life.

2017.11.20 | Annette Bang Rasmussen

Anna Starnawska, postdoc, Department of Biomedicine, Aarhus University and Shantel Weinsheimer, postdoc, Institute for Biological Psychiatry, Mental Health Centre Sct. Hans

About the study

We hypothesized that already at birth the epigenome of individuals with 22q11.2 deletion who have a psychiatric phenotype differs from those who carry the same deletion but do not have a psychiatric diagnosis. In this study, we performed the first Epigenome-Wide Association Study (EWAS) in neonatal blood spot samples for a large case cohort of 164 individuals with 22q11.2 deletion, including 29% with a psychiatric diagnosis. We identified several differentially methylated genes that associated with mental illness. Hence, epigenetic profiles in neonatal blood samples may prove to be a useful tool to identify, early on, which 22q11.2 deletion carriers are at increased risk for mental disorder, allowing for early intervention, as well as improved understanding of the pathogenesis that underlies development of psychiatric phenotypes.

The article "Differential DNA methylation at birth associated with mental disorder in individuals with 22q11.2 deletion syndrome" was published in Translational Psychiatry was published in Translational Psychiatry 2017 Aug 29;7(8).

Facts about the study

• We identified 9 differentially methylated CpG sites for psychiatric phenotype among 22q11.2 deletion carriers which mapped to 6 genes including STK32C, WDTC1, EFHD1, NUP93, NCAM1, and ZMYND10.
• EWAS of psychiatric sub-phenotypes identified additional differentially methylated genes associated with intellectual disability, behavioural disorders, disorders of psychological development and schizophrenia.
• The differentially methylated genes were enriched with those involved in neurogenesis, nervous development and neuron projection development.
• We detected alterations in genome-wide DNA methylation patterns associated with the type of 22q11.2 deletion.

Further information

Shantel Weinsheimer, Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Capital Region of Denmark. Email: shantel.marie.weinsheimer@regionh.dk

Anna Starnawska, Department of Biomedicine, Aarhus University. Email: as@biomed.au.dk