Investigation of correlations between DNA methylation, suicidal behavior and aging.
Bipolar Disord
; 19(1): 32-40, 2017 02.
Article
en En
| MEDLINE
| ID: mdl-28276657
ABSTRACT
OBJECTIVES:
Suicidal behavior (SB) is a major cause of mortality for patients diagnosed with bipolar disorder (BD). In this study, we investigated epigenetic differences in BD participants with and without a history of SB.METHODS:
We used suicidality scores constructed from Schedule for Clinical Assessments in Neuropsychiatry (SCAN) interview questions about suicidal thought and behavior to identify individuals from a BD cohort of n=452; participants with the most extreme high (H-SB, n=18) and most extreme low (L-SB, n=22) scores were used as cases and controls, respectively. Epigenome-wide DNA methylation patterns were compared between the two groups using the Illumina Infinium Human Methylation 450 BeadChip microarray. DNA methylation age was compared to chronological tissue age.RESULTS:
We observed highly significant differences in methylation between cases and controls in three genomic regions enriched for epigenetic modifications corresponding to gene regulatory regions. BD participants with a history of SB showed less overall methylation in the 5' untranslated region of Membrane palmitoylated protein 4 (MPP4) (P=7.42×10-7 ) and in intron 3 of TRE2/BUB2/CDC16 domain family member 16 (TBC1D16) (P=6.47×10-7 ), while exon 1 of Nucleoporin 133 (NUP133) was less methylated in controls (P=1.17x10-6 ). Moreover, we observed a greater correlation between DNA methylation age and tissue age in controls (r=.91, P<.0001) than in the H-SB group (r=.83, P<.0001).CONCLUSIONS:
We report significant findings at three loci based on a methylome scan of participants with BD for an SB phenotype, and potentially altered molecular aging in suicide attempters. Despite the small sample size, our proof-of-concept study highlights the potential for epigenetic factors to be useful in understanding the molecular underpinnings of suicide with the ultimate aim of its prevention.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Suicidio
/
Trastorno Bipolar
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Envejecimiento
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Antígenos de Histocompatibilidad Menor
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Nucleósido-Fosfato Quinasa
/
Proteínas Activadoras de GTPasa
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Proteínas de Complejo Poro Nuclear
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Proteínas del Ojo
/
Ideación Suicida
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Prevención del Suicidio
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Bipolar Disord
Asunto de la revista:
PSIQUIATRIA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Canadá