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Although most 22q11.2 deletion carriers have the long 3-Mb form of the hemizygous deletion, there remains a large variation in the development and progression of psychiatric disorders, which suggests that alternative factors contribute to the pathogenesis. In this study we investigated whether neonatal DNA methylation signatures in individuals with the 22q11.2 deletion associate with mental disorder later in life. DNA methylation was measured genome-wide from neonatal dried blood spots in a cohort of 164 individuals with 22q11.2DS, including 48 individuals diagnosed with a psychiatric disorder. Among several CpG sites with<jats:italic>P<\/jats:italic>-value&lt;10<jats:sup>\u22126<\/jats:sup>, we identified cg23546855 (<jats:italic>P<\/jats:italic>-value=2.15 \u00d7 10<jats:sup>\u22127<\/jats:sup>) mapping to<jats:italic>STK32C<\/jats:italic>to be associated with a later psychiatric diagnosis. Pathway analysis of the top findings resulted in the identification of several Gene Ontology pathways to be significantly enriched (<jats:italic>P<\/jats:italic>-value&lt;0.05 after Benjamini\u2013Hochberg correction); among them are the following: neurogenesis, neuron development, neuron projection development, astrocyte development, axonogenesis and axon guidance. In addition, we identified differentially methylated CpG sites in<jats:italic>LRP2BP<\/jats:italic>(<jats:italic>P<\/jats:italic>-value=5.37 \u00d7 10<jats:sup>\u22128<\/jats:sup>) to be associated with intellectual disability (F70\u201379), in<jats:italic>TOP1<\/jats:italic>(<jats:italic>P<\/jats:italic>-value=1.86 \u00d7 10<jats:sup>\u22127<\/jats:sup>) with behavioral disorders (F90\u201398), in<jats:italic>NOSIP<\/jats:italic>(<jats:italic>P<\/jats:italic>-value=5.12 \u00d7 10<jats:sup>\u22128<\/jats:sup>) with disorders of psychological development (F80\u201389) and in<jats:italic>SEMA4B<\/jats:italic>(<jats:italic>P<\/jats:italic>-value=4.02 \u00d7 10<jats:sup>\u22127<\/jats:sup>) with schizophrenia spectrum disorders (F20\u201329). In conclusion, our study suggests an association of DNA methylation differences at birth with development of mental disorder later in life in 22q11.2DS individuals.<\/jats:p>","DOI":"10.1038\/tp.2017.181","type":"journal-article","created":{"date-parts":[[2017,8,29]],"date-time":"2017-08-29T13:42:06Z","timestamp":1504014126000},"page":"e1221-e1221","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Differential DNA methylation at birth associated with mental disorder in individuals with 22q11.2 deletion syndrome"],"prefix":"10.1038","volume":"7","author":[{"given":"A","family":"Starnawska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C S","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Spars\u00f8","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W","family":"Mazin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Olsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Bertalan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Buil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Bybjerg-Grauholm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"B\u00e6kvad-Hansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D M","family":"Hougaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P B","family":"Mortensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C B","family":"Pedersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Nyegaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Werge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Weinsheimer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,8,29]]},"reference":[{"key":"BFtp2017181_CR1","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1176\/appi.ajp.2013.13070864","volume":"171","author":"M Schneider","year":"2014","unstructured":"Schneider M, Debban\u00e9 M, Bassett AS, Chow EWC, Fung WLA, van den Bree M et al. 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