Nine differentially expressed genes from a post mortem study and their association with suicidal status in a sample of suicide completers, attempters and controls.
Several lines of evidence indicate that suicidal behaviour is partly heritable, with multiple genes implicated in its aetiology. We focused on nine genes (S100A13, EFEMP1, PCDHB5, PDGFRB, CDCA7L, SCN2B, PTPRR, MLC1 and ZFP36) which we previously detected as differentially expressed in the cortex of suicide victims compared to controls. We investigated 84 variants within these genes in 495 suicidal subjects (299 completers and 196 attempters) and 1513 controls (109 post-mortem and 1404 healthy). We evaluated associations with: 1) suicidal phenotype; 2) possible endophenotypes for suicidal behaviour. Overall positive results did not survive the correction threshold. However, we found a nominally different distribution of EFEMP1 genotypes, alleles and haplotypes between suicidal subjects and controls, results that were partially replicated when we separately considered the subgroup of suicide completers and post-mortem controls. A weaker association emerged also for PTPRR. Both EFEMP1 and PTPRR genes were also related to possible endophenotypes for suicidal behaviour such as anger, depression-anxiety and fatigue. Because of the large number of analyses performed and the low significance values further replication are mandatory. Nevertheless, neurotrophic gene variants, in particular EFEMP1 and PTPRR, may have a role in the pathogenesis of suicidal behaviour.
Department of Biomedical and NeuroMotor Sciences, University of Bologna, Italy.
Martina
M
Balestri
Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Italy.
Concetta
C
Crisafulli
Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Italy.
Luigi
L
Donato
Department of Psychiatry, University of Halle, Germany.
Ina
I
Giegling
INSERM U1061, University of Montpellier, FondaMental Foundation, Montpellier, France.
Raffaella
R
Calati
Department of Biomedical and NeuroMotor Sciences, University of Bologna, Italy.
Niki
N
Antypa
Department of Addiction, LVR-Clinic, Cologne, Germany.
Barbara
B
Schneider
Mental Health Department, PINT, University of Primorska, Primorska, Slovenia.
Dragan
D
Marusic
Department of Biomedical and NeuroMotor Sciences, University of Bologna, Italy.
Maria Eugenia
ME
Tarozzi
Mental Health Department, PINT, University of Primorska, Primorska, Slovenia.
Dorjan
D
Marusic
Institute of Public Health of the Republic of Slovenia, Slovenia.
Metka
M
Paragi
Department of Psychiatry, University of Halle, Germany.
Annette M
AM
Hartmann
Department of Psychiatry, University of Halle, Germany.
Bettina
B
Konte
Department of Biomedical and NeuroMotor Sciences, University of Bologna, Italy.
Agnese
A
Marsano
Department of Biomedical and NeuroMotor Sciences, University of Bologna, Italy. Electronic address: alessandro.serretti@unibo.it.
Alessandro
A
Serretti
Department of Psychiatry, University of Halle, Germany.
Dan
D
Rujescu
D000328:Adult; D000368:Aged; D001344:Autopsy; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D054634:Receptor-Like Protein Tyrosine Phosphatases, Class 7 / Q000235:genetics*; D016728:Self-Injurious Behavior / Q000235:genetics* / Q000523:psychology; D059020:Suicidal Ideation; D013405:Suicide / Q000523:psychology*; D013406:Suicide, Attempted / Q000523:psychology*; D011795:Surveys and Questionnaires
C119630:EFEMP1 protein, human; D016326:Extracellular Matrix Proteins; C513469:PTPRR protein, human; D054634:Receptor-Like Protein Tyrosine Phosphatases, Class 7
Candidate genes; Personality; Post-mortem; Suicide