A genome-wide association study of suicide severity scores in bipolar disorder.
BACKGROUND
Suicide claims one million lives worldwide annually, making it a serious public health concern. The risk for suicidal behaviour can be partly explained by genetic factors, as suggested by twin and family studies (reviewed in (Zai et al. 2012)). Recently, genome-wide association studies (GWASs) of suicide attempt on large samples of bipolar disorder (BD) patients from multiple sites have identified a number of novel candidate genes. GWASs of suicide behaviour severity, from suicidal ideation to serious suicide attempt, have not been reported for BD.


METHODS
We conducted a GWAS of suicide behaviour severity in three independent BD samples:212 small nuclear families with BD probands from Toronto, Canada, 428 BD cases from Toronto, and 483 BD cases from the UK. We carried out imputation with 1000 Genome Project data as reference using IMPUTE2. Quality control and data analysis was conducted using PLINK and R. We conducted the quantitative analyses of suicide behaviour severity in the three samples separately, and derived an overall significance by a meta-analysis using the METAL software.


RESULTS
We did not find genome-wide significant association of any tested markers in any of the BD samples, but we found a number of suggestive associations, including regions on chromosomes 8 and 10 (p < 1e-5).


CONCLUSIONS
Our GWAS findings suggest that likely many gene variants of small effects contribute collectively to the risk for suicidal behaviour severity in BD. Larger independent replications are required to strengthen the findings from the GWAS presented here.
Neurogenetics Section, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Clement C
CC
Zai
Neurogenetics Section, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Vanessa F
VF
Gonçalves
Neurogenetics Section, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Arun K
AK
Tiwari
Neurogenetics Section, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Ontario, Canada.
Sarah A
SA
Gagliano
Department of Psychology, Goldsmiths, University of London, New Cross, London, United Kingdom; MRC Social, Genetic & Developmental Psychiatry Centre, King's College London, London, United Kingdom.
Georgina
G
Hosang
Neurogenetics Section, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Ontario, Canada.
Vincenzo
V
de Luca
Neurogenetics Section, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Sajid A
SA
Shaikh
Neurogenetics Section, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Nicole
N
King
Cancer Care Ontario, Toronto, Ontario, Canada.
Qian
Q
Chen
Dalla Lana School of Public Health, University of Toronto, Ontario, Canada; Ontario Cancer Institute, Prince Margaret Hospital, Toronto, Ontario, Canada.
Wei
W
Xu
Neurogenetics Section, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
John
J
Strauss
MRC Social, Genetic & Developmental Psychiatry Centre, King's College London, London, United Kingdom.
Gerome
G
Breen
MRC Social, Genetic & Developmental Psychiatry Centre, King's College London, London, United Kingdom.
Cathryn M
CM
Lewis
MRC Social, Genetic & Developmental Psychiatry Centre, King's College London, London, United Kingdom.
Anne E
AE
Farmer
MRC Social, Genetic & Developmental Psychiatry Centre, King's College London, London, United Kingdom.
Peter
P
McGuffin
Neurogenetics Section, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Ontario, Canada.
Jo
J
Knight
Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Ontario, Canada; Molecular Neuropsychiatry and Development Laboratory (MiND), Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
John B
JB
Vincent
Neurogenetics Section, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Ontario, Canada. Electronic address: jim.kennedy@camh.ca.
James L
JL
Kennedy
D001714:Bipolar Disorder / Q000235:genetics* / Q000523:psychology*; D002170:Canada; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013405:Suicide / Q000523:psychology*
Bipolar disorder; Genome-wide association study; Imputation; Meta-analysis; Suicidal behaviour severity; Suicide attempt