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

Hdl Handle:
http://hdl.handle.net/10147/333814
Title:
Genetic variation in DNMT3B and increased global DNA methylation is associated with suicide attempts in psychiatric patients
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.
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
Issue Date:
Sep-2012
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
Keywords:
PATHOLOGY; SUICIDE
ISSN:
16011848

Full metadata record

DC FieldValue Language
dc.contributor.authorMurphy, T. M.en_GB
dc.contributor.authorMullins, N.en_GB
dc.contributor.authorRyan, M.en_GB
dc.contributor.authorFoster, T.en_GB
dc.contributor.authorKelly, C.en_GB
dc.contributor.authorMcClelland, R.en_GB
dc.contributor.authorO'Grady, J.en_GB
dc.contributor.authorCorcoran, E.en_GB
dc.contributor.authorBrady, J.en_GB
dc.contributor.authorReilly, M.en_GB
dc.contributor.authorJeffers, A.en_GB
dc.contributor.authorBrown, K.en_GB
dc.contributor.authorMaher, A.en_GB
dc.contributor.authorBannan, N.en_GB
dc.contributor.authorCasement, A.en_GB
dc.contributor.authorLynch, D.en_GB
dc.contributor.authorBolger, S.en_GB
dc.contributor.authorBuckley, A.en_GB
dc.contributor.authorQuinlivan, L.en_GB
dc.contributor.authorDaly, L.en_GB
dc.contributor.authorKelleher, C.en_GB
dc.contributor.authorMalone, K. M.en_GB
dc.date.accessioned2014-11-07T12:22:09Z-
dc.date.available2014-11-07T12:22:09Z-
dc.date.issued2012-09-
dc.identifier.citationGenetic variation in DNMT3B and increased global DNA methylation is associated with suicide attempts in psychiatric patients 2013, 12 (1):125 Genes, Brain and Behavioren_GB
dc.identifier.issn16011848-
dc.identifier.doi10.1111/j.1601-183X.2012.00865.x-
dc.identifier.urihttp://hdl.handle.net/10147/333814-
dc.description.abstractRecently, 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.en_GB
dc.language.isoenen
dc.publisherGenes, Brain and Behavioren_GB
dc.relation.urlhttp://doi.wiley.com/10.1111/j.1601-183X.2012.00865.xen_GB
dc.rightsArchived with thanks to Genes, Brain and Behavioren_GB
dc.subjectPATHOLOGYen_GB
dc.subjectSUICIDEen_GB
dc.titleGenetic variation in DNMT3B and increased global DNA methylation is associated with suicide attempts in psychiatric patientsen_GB
dc.typeArticleen
dc.identifier.journalGenes, Brain and Behavioren_GB
dc.description.fundingNo fundingen
dc.description.provinceLeinsteren
dc.description.peer-reviewpeer-reviewen
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