Discovery and replication of a peripheral tissue DNA methylation biosignature to augment a suicide prediction model

Makena L Clive, Marco P Boks, Christiaan H Vinkers, Lauren M Osborne, Jennifer L Payne, Kerry J Ressler, Alicia K Smith, Holly C Wilcox, Zachary Kaminsky

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: Suicide is the second leading cause of death among adolescents in the USA, and rates are rising. Methods to identify individuals at risk are essential for implementing prevention strategies, and the development of a biomarker can potentially improve prediction of suicidal behaviors. Prediction of our previously reported SKA2 biomarker for suicide and PTSD is substantially improved by questionnaires assessing perceived stress or anxiety and is therefore reliant on psychological assessment. However, such stress-related states may also leave a biosignature that could equally improve suicide prediction. In genome-wide DNA methylation data, we observed significant overlap between waking cortisol-associated and suicide-associated DNA methylation in blood and the brain, respectively.

RESULTS: Using a custom bioinformatic brain to blood discovery algorithm, we derived a DNA methylation biosignature that interacts with SKA2 methylation to improve the prediction of suicidal ideation in our existing suicide prediction model across both blood and saliva data sets. This biosignature was independently validated in the Grady Trauma Project cohort and interacted with HPA axis metrics in the same cohort. The biosignature showed a relationship with immune status by its correlation with myeloid-derived cell proportions in all data sets and with IL-6 measures in a prospective postpartum depression cohort. Three probes showed significant correlations with the biosignature: cg08469255 (DDR1), cg22029879 (ARHGEF10), and cg24437859 (SHP1), of which SHP1 methylation correlated with immune measures.

CONCLUSIONS: We conclude that this biosignature interacts with SKA2 methylation to improve suicide prediction and may represent a biological state of immune and HPA axis modulation that mediates suicidal behavior.

Original languageEnglish
Pages (from-to)113
JournalClinical epigenetics
Volume8
DOIs
Publication statusPublished - 2016

Cite this

Clive, Makena L ; Boks, Marco P ; Vinkers, Christiaan H ; Osborne, Lauren M ; Payne, Jennifer L ; Ressler, Kerry J ; Smith, Alicia K ; Wilcox, Holly C ; Kaminsky, Zachary. / Discovery and replication of a peripheral tissue DNA methylation biosignature to augment a suicide prediction model. In: Clinical epigenetics. 2016 ; Vol. 8. pp. 113.
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abstract = "BACKGROUND: Suicide is the second leading cause of death among adolescents in the USA, and rates are rising. Methods to identify individuals at risk are essential for implementing prevention strategies, and the development of a biomarker can potentially improve prediction of suicidal behaviors. Prediction of our previously reported SKA2 biomarker for suicide and PTSD is substantially improved by questionnaires assessing perceived stress or anxiety and is therefore reliant on psychological assessment. However, such stress-related states may also leave a biosignature that could equally improve suicide prediction. In genome-wide DNA methylation data, we observed significant overlap between waking cortisol-associated and suicide-associated DNA methylation in blood and the brain, respectively.RESULTS: Using a custom bioinformatic brain to blood discovery algorithm, we derived a DNA methylation biosignature that interacts with SKA2 methylation to improve the prediction of suicidal ideation in our existing suicide prediction model across both blood and saliva data sets. This biosignature was independently validated in the Grady Trauma Project cohort and interacted with HPA axis metrics in the same cohort. The biosignature showed a relationship with immune status by its correlation with myeloid-derived cell proportions in all data sets and with IL-6 measures in a prospective postpartum depression cohort. Three probes showed significant correlations with the biosignature: cg08469255 (DDR1), cg22029879 (ARHGEF10), and cg24437859 (SHP1), of which SHP1 methylation correlated with immune measures.CONCLUSIONS: We conclude that this biosignature interacts with SKA2 methylation to improve suicide prediction and may represent a biological state of immune and HPA axis modulation that mediates suicidal behavior.",
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journal = "Clinical epigenetics",
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Discovery and replication of a peripheral tissue DNA methylation biosignature to augment a suicide prediction model. / Clive, Makena L; Boks, Marco P; Vinkers, Christiaan H; Osborne, Lauren M; Payne, Jennifer L; Ressler, Kerry J; Smith, Alicia K; Wilcox, Holly C; Kaminsky, Zachary.

In: Clinical epigenetics, Vol. 8, 2016, p. 113.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Discovery and replication of a peripheral tissue DNA methylation biosignature to augment a suicide prediction model

AU - Clive, Makena L

AU - Boks, Marco P

AU - Vinkers, Christiaan H

AU - Osborne, Lauren M

AU - Payne, Jennifer L

AU - Ressler, Kerry J

AU - Smith, Alicia K

AU - Wilcox, Holly C

AU - Kaminsky, Zachary

PY - 2016

Y1 - 2016

N2 - BACKGROUND: Suicide is the second leading cause of death among adolescents in the USA, and rates are rising. Methods to identify individuals at risk are essential for implementing prevention strategies, and the development of a biomarker can potentially improve prediction of suicidal behaviors. Prediction of our previously reported SKA2 biomarker for suicide and PTSD is substantially improved by questionnaires assessing perceived stress or anxiety and is therefore reliant on psychological assessment. However, such stress-related states may also leave a biosignature that could equally improve suicide prediction. In genome-wide DNA methylation data, we observed significant overlap between waking cortisol-associated and suicide-associated DNA methylation in blood and the brain, respectively.RESULTS: Using a custom bioinformatic brain to blood discovery algorithm, we derived a DNA methylation biosignature that interacts with SKA2 methylation to improve the prediction of suicidal ideation in our existing suicide prediction model across both blood and saliva data sets. This biosignature was independently validated in the Grady Trauma Project cohort and interacted with HPA axis metrics in the same cohort. The biosignature showed a relationship with immune status by its correlation with myeloid-derived cell proportions in all data sets and with IL-6 measures in a prospective postpartum depression cohort. Three probes showed significant correlations with the biosignature: cg08469255 (DDR1), cg22029879 (ARHGEF10), and cg24437859 (SHP1), of which SHP1 methylation correlated with immune measures.CONCLUSIONS: We conclude that this biosignature interacts with SKA2 methylation to improve suicide prediction and may represent a biological state of immune and HPA axis modulation that mediates suicidal behavior.

AB - BACKGROUND: Suicide is the second leading cause of death among adolescents in the USA, and rates are rising. Methods to identify individuals at risk are essential for implementing prevention strategies, and the development of a biomarker can potentially improve prediction of suicidal behaviors. Prediction of our previously reported SKA2 biomarker for suicide and PTSD is substantially improved by questionnaires assessing perceived stress or anxiety and is therefore reliant on psychological assessment. However, such stress-related states may also leave a biosignature that could equally improve suicide prediction. In genome-wide DNA methylation data, we observed significant overlap between waking cortisol-associated and suicide-associated DNA methylation in blood and the brain, respectively.RESULTS: Using a custom bioinformatic brain to blood discovery algorithm, we derived a DNA methylation biosignature that interacts with SKA2 methylation to improve the prediction of suicidal ideation in our existing suicide prediction model across both blood and saliva data sets. This biosignature was independently validated in the Grady Trauma Project cohort and interacted with HPA axis metrics in the same cohort. The biosignature showed a relationship with immune status by its correlation with myeloid-derived cell proportions in all data sets and with IL-6 measures in a prospective postpartum depression cohort. Three probes showed significant correlations with the biosignature: cg08469255 (DDR1), cg22029879 (ARHGEF10), and cg24437859 (SHP1), of which SHP1 methylation correlated with immune measures.CONCLUSIONS: We conclude that this biosignature interacts with SKA2 methylation to improve suicide prediction and may represent a biological state of immune and HPA axis modulation that mediates suicidal behavior.

KW - Adolescent

KW - Chromosomal Proteins, Non-Histone/genetics

KW - Computational Biology/methods

KW - DNA Methylation

KW - Discoidin Domain Receptor 1/genetics

KW - Female

KW - Genetic Markers/genetics

KW - Genome-Wide Association Study

KW - Health Surveys

KW - Humans

KW - Male

KW - Models, Psychological

KW - Oligonucleotide Array Sequence Analysis/methods

KW - Protein Tyrosine Phosphatase, Non-Receptor Type 6/genetics

KW - Rho Guanine Nucleotide Exchange Factors/genetics

KW - Risk Assessment

KW - Stress Disorders, Post-Traumatic/psychology

KW - Suicidal Ideation

KW - Suicide/psychology

U2 - 10.1186/s13148-016-0279-1

DO - 10.1186/s13148-016-0279-1

M3 - Article

VL - 8

SP - 113

JO - Clinical epigenetics

JF - Clinical epigenetics

SN - 1868-7083

ER -