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    Genetic variation in DNMT3B and increased global DNA methylation is associated with suicide attempts in psychiatric patients

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    Authors
    Murphy, T. M.
    Mullins, N.
    Ryan, M.
    Foster, T.
    Kelly, C.
    McClelland, R.
    O'Grady, J.
    Corcoran, E.
    Brady, J.
    Reilly, M.
    Jeffers, A.
    Brown, K.
    Maher, A.
    Bannan, N.
    Casement, A.
    Lynch, D.
    Bolger, S.
    Buckley, A.
    Quinlivan, L.
    Daly, L.
    Kelleher, C.
    Malone, K. M.
    Show allShow less
    Issue Date
    2012-09
    Keywords
    PATHOLOGY
    SUICIDE
    
    Metadata
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    Citation
    Genetic variation in DNMT3B and increased global DNA methylation is associated with suicide attempts in psychiatric patients 2013, 12 (1):125 Genes, Brain and Behavior
    Publisher
    Genes, Brain and Behavior
    Journal
    Genes, Brain and Behavior
    URI
    http://hdl.handle.net/10147/333814
    DOI
    10.1111/j.1601-183X.2012.00865.x
    Additional Links
    http://doi.wiley.com/10.1111/j.1601-183X.2012.00865.x
    Abstract
    Recently, a significant epigenetic component in the pathology of suicide has been realized. Here we investigate candidate functional SNPs in epigenetic-regulatory genes, DNMT1 and DNMT3B, for association with suicide attempt (SA) among patients with co-existing psychiatric illness. In addition, global DNA methylation levels [5-methyl cytosine (5-mC%)] between SA and psychiatric controls were quantified using the Methylflash Methylated DNA Quantification Kit. DNA was obtained from blood of 79 suicide attempters and 80 non-attempters, assessed for DSM-IV Axis I disorders. Functional SNPs were selected for each gene (DNMT1; n =7, DNMT3B; n =10), and genotyped. A SNP (rs2424932) residing in the 3 UTR of the DNMT3B gene was associated with SA compared with a non-attempter control group (P =0.001; Chi-squared test, Bonferroni adjusted P value=0.02). Moreover, haplotype analysis identified a DNMT3B haplotype which differed between cases and controls, however this association did not hold after Bonferroni correction (P =0.01, Bonferroni adjusted P value=0.56). Global methylation analysis showed that psychiatric patientswith a history of SA had significantly higher levels of global DNA methylation compared with controls (P =0.018, Student’s t -test). In conclusion, this is the first report investigating polymorphisms in DNMT genes and global DNA methylation quantification in SA risk. Preliminary findings suggest that allelic variability in DNMT3B may be relevant to the underlying diathesis for suicidal acts and our findings support the hypothesis that aberrant DNA methylation profiles may contribute to the biology of suicidal acts. Thus, analysis of global DNA hypermethylation in blood may represent a biomarker for increased SA risk in psychiatric patients.
    Item Type
    Article
    Language
    en
    ISSN
    16011848
    ae974a485f413a2113503eed53cd6c53
    10.1111/j.1601-183X.2012.00865.x
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