Association analysis between suicidal behaviour and candidate genes of bipolar disorder and schizophrenia.
BACKGROUND
The present study investigated associations between the strongest joint genetic risk variants for bipolar disorder (BD) and schizophrenia (SCZ) and a history of suicide attempt in patients with BD, SCZ and related psychiatric disorders.


METHODS
A history of suicide attempt was assessed in a sample of 1009 patients with BD, SCZ and related psychosis spectrum disorders, and associations with the joint genetic risk variants for BD and SCZ (rs2239547 (ITIH3/4-region), rs10994359 (ANK3) and rs4765905 (CACNA1C)) were investigated. Previously reported susceptibility loci for suicide attempt in BD were also investigated. Associations were tested by logistic regression with Bonferroni correction for multiple testing.


RESULTS
The risk allele in rs2239547 (ITIH3/4-region) was significantly associated with a history of suicide attempt (p=0.01) after multiple testing correction (p threshold<0.017). The previous suicide attempt susceptibility loci were only nominally associated, but had the same direction of risk in the replication sample (sign test, p=0.02).


CONCLUSIONS
Relatively small sample size and retrospective clinical assessment.


CONCLUSIONS
We detected a novel association between suicide attempt and the ITIH3/4-region in a combined group of patients with BD, SCZ and related psychosis spectrum disorders. This may be useful in understanding molecular mechanisms of suicidal behaviour in severe mental disorders, although replication is warranted.
Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Østmarka Psychiatric Department, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway. Electronic address: per.i.finseth@ntnu.no.
Per Ivar
PI
Finseth
Department of Medical Genetics, Oslo University Hospital, Oslo, Norway; K. G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Ida Elken
IE
Sønderby
Department of Medical Genetics, Oslo University Hospital, Oslo, Norway; K. G. Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Srdjan
S
Djurovic
K. G. Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
Ingrid
I
Agartz
Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Neuropsychiatry and Psychosomatic Medicine, Division of Surgery and Neuroscience, Oslo University Hospital, Oslo, Norway.
Ulrik Fredrik
UF
Malt
K. G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; K. G. Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Ingrid
I
Melle
Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Department of Research and Development, Psychiatry, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
Gunnar
G
Morken
K. G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; K. G. Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Ole Andreas
OA
Andreassen
Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Østmarka Psychiatric Department, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
Arne Einar
AE
Vaaler
K. G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; K. G. Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Martin
M
Tesli
D000328:Adult; D000483:Alleles; D000510:Alpha-Globulins / Q000235:genetics*; D017487:Ankyrins / Q000235:genetics; D001714:Bipolar Disorder / Q000235:genetics* / Q000523:psychology; D001798:Blood Proteins / Q000235:genetics*; D020746:Calcium Channels, L-Type / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D053491:Proteinase Inhibitory Proteins, Secretory / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics*; D012565:Schizophrenic Psychology; D059020:Suicidal Ideation; D013406:Suicide, Attempted / Q000523:psychology
C490613:ANK3 protein, human; D000510:Alpha-Globulins; D017487:Ankyrins; D001798:Blood Proteins; C079146:CACNA1C protein, human; D020746:Calcium Channels, L-Type; D006023:Glycoproteins; C091236:ITIH4 protein, human; D053491:Proteinase Inhibitory Proteins, Secretory; C011877:inter-alpha-inhibitor
Bipolar disorder; Candidate gene; Schizophrenia; Suicidal behaviour