Journal article
Differentially methylated regions in bipolar disorder and suicide
American journal of medical genetics. Part B, Neuropsychiatric genetics, Vol.180(7), pp.496-507
10/2019
DOI: 10.1002/ajmg.b.32754
PMID: 31350827
Abstract
The addition of a methyl group to, typically, a cytosine-guanine dinucleotide (CpG) creates distinct DNA methylation patterns across the genome that can regulate gene expression. Aberrant DNA methylation of CpG sites has been associated with many psychiatric disorders including bipolar disorder (BD) and suicide. Using the SureSelectXT system, Methyl-Seq, we investigated the DNA methylation status of CpG sites throughout the genome in 50 BD individuals (23 subjects who died by suicide and 27 subjects who died from other causes) and 31 nonpsychiatric controls. We identified differentially methylated regions (DMRs) from three analyses: (a) BD subjects compared to nonpsychiatric controls (BD-NC), (b) BD subjects who died by suicide compared to nonpsychiatric controls (BDS-NC), and (c) BDS subjects compared to BD subjects who died from other causes (BDS-BDNS). One DMR from the BDS-NC analysis, located in ARHGEF38, was significantly hypomethylated (23.4%) in BDS subjects. This finding remained significant after multiple testing (PBootstrapped = 9.0 × 10-3 ), was validated using pyrosequencing, and was more significant in males. A secondary analysis utilized Ingenuity Pathway Analysis to identify enrichment in nominally significant DMRs. This identified an association with several pathways including axonal guidance signaling, calcium signaling, β-adrenergic signaling, and opioid signaling. Our comprehensive study provides further support that DNA methylation alterations influence the risk for BD and suicide. However, further investigation is required to confirm these associations and identify their functional consequences.
Details
- Title: Subtitle
- Differentially methylated regions in bipolar disorder and suicide
- Creators
- Marie E Gaine - Department of PsychiatryUniversity of Iowa Carver College of Medicine Iowa City IowaFayaz Seifuddin - Department of Psychiatry and Behavioral SciencesJohns Hopkins School of Medicine Baltimore MarylandSarven Sabunciyan - Center for EpigeneticsJohns Hopkins School of Medicine Baltimore Maryland, Department of PediatricsJohns Hopkins School of Medicine Baltimore MarylandRichard S Lee - Department of Psychiatry and Behavioral SciencesJohns Hopkins School of Medicine Baltimore MarylandKelly S Benke - Department of Mental Health, Bloomberg School of Public HealthJohns Hopkins University Baltimore MarylandEric T Monson - Department of PsychiatryUniversity of Iowa Carver College of Medicine Iowa City IowaPeter P Zandi - Department of Psychiatry and Behavioral SciencesJohns Hopkins School of Medicine Baltimore Maryland, Department of Mental Health, Bloomberg School of Public HealthJohns Hopkins University Baltimore MarylandJames B Potash - Department of Psychiatry and Behavioral SciencesJohns Hopkins School of Medicine Baltimore MarylandVirginia L Willour - Department of PsychiatryUniversity of Iowa Carver College of Medicine Iowa City Iowa
- Resource Type
- Journal article
- Publication Details
- American journal of medical genetics. Part B, Neuropsychiatric genetics, Vol.180(7), pp.496-507
- DOI
- 10.1002/ajmg.b.32754
- PMID
- 31350827
- NLM abbreviation
- Am J Med Genet B Neuropsychiatr Genet
- ISSN
- 1552-4841
- eISSN
- 1552-485X
- Grant note
- DOI: 10.13039/100001455, name: American Foundation for Suicide Prevention, award: Postdoctoral Fellowship Grant PDF‐0‐067‐12; DOI: 10.13039/100000025, name: National Institute of Mental Health, award: R21 MH096154
- Language
- English
- Date published
- 10/2019
- Academic Unit
- Psychiatry; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984070795602771
Metrics
22 Record Views