Multimarker analysis suggests the involvement of BDNF signaling and microRNA biosynthesis in suicidal behavior

Attila J. Pulay, J. Réthelyi

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Despite moderate heritability estimates the genetics of suicidal behavior remains unclear, genome-wide association and candidate gene studies focusing on single nucleotide associations reported inconsistent findings. Our study explored biologically informed, multimarker candidate gene associations with suicidal behavior in mood disorders. We analyzed the GAIN Whole Genome Association Study of Bipolar Disorder version 3 (n=999, suicidal n=358) and the GAIN Major Depression: Stage 1 Genomewide Association in Population-Based Samples (n=1,753, suicidal n=245) datasets. Suicidal behavior was defined as severe suicidal ideation or attempt. Candidate genes were selected based on literature search (Geneset1, n=35), gene expression data of microRNA genes, (Geneset2, n=68) and their target genes (Geneset3, n=11,259). Quality control, dosage analyses were carried out with PLINK. Gene-based associations of Geneset1 were analyzed with KGG. Polygenic profile scores of suicidal behavior were computed in the major depression dataset both with PRSice and LDpred and validated in the bipolar disorder data. Several nominally significant gene-based associations were detected, but only DICER1 associated with suicidal behavior in both samples, while only the associations of NTRK2 in the depression sample reached family wise and experiment wise significance. Polygenic profile scores negatively predicted suicidal behavior in the bipolar sample for only Geneset2, with the strongest prediction by PRSice at Pt2=0.01, P

Original languageEnglish
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
DOIs
Publication statusAccepted/In press - 2016

Fingerprint

Brain-Derived Neurotrophic Factor
MicroRNAs
Genes
Depression
Bipolar Disorder
Suicidal Ideation
Genome-Wide Association Study
Genetic Association Studies
Mood Disorders
Quality Control
Nucleotides
Genome
Gene Expression
Population

Keywords

  • Bayesian PRS
  • Executive functions
  • Polygenic risk score
  • Region-based heritability
  • Suicidal behavior

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

@article{eb1074904148470d9728687ddb4d86d3,
title = "Multimarker analysis suggests the involvement of BDNF signaling and microRNA biosynthesis in suicidal behavior",
abstract = "Despite moderate heritability estimates the genetics of suicidal behavior remains unclear, genome-wide association and candidate gene studies focusing on single nucleotide associations reported inconsistent findings. Our study explored biologically informed, multimarker candidate gene associations with suicidal behavior in mood disorders. We analyzed the GAIN Whole Genome Association Study of Bipolar Disorder version 3 (n=999, suicidal n=358) and the GAIN Major Depression: Stage 1 Genomewide Association in Population-Based Samples (n=1,753, suicidal n=245) datasets. Suicidal behavior was defined as severe suicidal ideation or attempt. Candidate genes were selected based on literature search (Geneset1, n=35), gene expression data of microRNA genes, (Geneset2, n=68) and their target genes (Geneset3, n=11,259). Quality control, dosage analyses were carried out with PLINK. Gene-based associations of Geneset1 were analyzed with KGG. Polygenic profile scores of suicidal behavior were computed in the major depression dataset both with PRSice and LDpred and validated in the bipolar disorder data. Several nominally significant gene-based associations were detected, but only DICER1 associated with suicidal behavior in both samples, while only the associations of NTRK2 in the depression sample reached family wise and experiment wise significance. Polygenic profile scores negatively predicted suicidal behavior in the bipolar sample for only Geneset2, with the strongest prediction by PRSice at Pt2=0.01, P",
keywords = "Bayesian PRS, Executive functions, Polygenic risk score, Region-based heritability, Suicidal behavior",
author = "Pulay, {Attila J.} and J. R{\'e}thelyi",
year = "2016",
doi = "10.1002/ajmg.b.32433",
language = "English",
journal = "American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics",
issn = "1552-4841",
publisher = "Wiley-Liss Inc.",

}

TY - JOUR

T1 - Multimarker analysis suggests the involvement of BDNF signaling and microRNA biosynthesis in suicidal behavior

AU - Pulay, Attila J.

AU - Réthelyi, J.

PY - 2016

Y1 - 2016

N2 - Despite moderate heritability estimates the genetics of suicidal behavior remains unclear, genome-wide association and candidate gene studies focusing on single nucleotide associations reported inconsistent findings. Our study explored biologically informed, multimarker candidate gene associations with suicidal behavior in mood disorders. We analyzed the GAIN Whole Genome Association Study of Bipolar Disorder version 3 (n=999, suicidal n=358) and the GAIN Major Depression: Stage 1 Genomewide Association in Population-Based Samples (n=1,753, suicidal n=245) datasets. Suicidal behavior was defined as severe suicidal ideation or attempt. Candidate genes were selected based on literature search (Geneset1, n=35), gene expression data of microRNA genes, (Geneset2, n=68) and their target genes (Geneset3, n=11,259). Quality control, dosage analyses were carried out with PLINK. Gene-based associations of Geneset1 were analyzed with KGG. Polygenic profile scores of suicidal behavior were computed in the major depression dataset both with PRSice and LDpred and validated in the bipolar disorder data. Several nominally significant gene-based associations were detected, but only DICER1 associated with suicidal behavior in both samples, while only the associations of NTRK2 in the depression sample reached family wise and experiment wise significance. Polygenic profile scores negatively predicted suicidal behavior in the bipolar sample for only Geneset2, with the strongest prediction by PRSice at Pt2=0.01, P

AB - Despite moderate heritability estimates the genetics of suicidal behavior remains unclear, genome-wide association and candidate gene studies focusing on single nucleotide associations reported inconsistent findings. Our study explored biologically informed, multimarker candidate gene associations with suicidal behavior in mood disorders. We analyzed the GAIN Whole Genome Association Study of Bipolar Disorder version 3 (n=999, suicidal n=358) and the GAIN Major Depression: Stage 1 Genomewide Association in Population-Based Samples (n=1,753, suicidal n=245) datasets. Suicidal behavior was defined as severe suicidal ideation or attempt. Candidate genes were selected based on literature search (Geneset1, n=35), gene expression data of microRNA genes, (Geneset2, n=68) and their target genes (Geneset3, n=11,259). Quality control, dosage analyses were carried out with PLINK. Gene-based associations of Geneset1 were analyzed with KGG. Polygenic profile scores of suicidal behavior were computed in the major depression dataset both with PRSice and LDpred and validated in the bipolar disorder data. Several nominally significant gene-based associations were detected, but only DICER1 associated with suicidal behavior in both samples, while only the associations of NTRK2 in the depression sample reached family wise and experiment wise significance. Polygenic profile scores negatively predicted suicidal behavior in the bipolar sample for only Geneset2, with the strongest prediction by PRSice at Pt2=0.01, P

KW - Bayesian PRS

KW - Executive functions

KW - Polygenic risk score

KW - Region-based heritability

KW - Suicidal behavior

UR - http://www.scopus.com/inward/record.url?scp=84959440273&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84959440273&partnerID=8YFLogxK

U2 - 10.1002/ajmg.b.32433

DO - 10.1002/ajmg.b.32433

M3 - Article

C2 - 26921221

AN - SCOPUS:84959440273

JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

SN - 1552-4841

ER -