Final published version
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - A genome-wide association study of suicide severity scores in bipolar disorder
AU - Zai, Clement C.
AU - Gonçalves, Vanessa F.
AU - Tiwari, Arun K.
AU - Gagliano, Sarah A.
AU - Hosang, Georgina
AU - de Luca, Vincenzo
AU - Shaikh, Sajid A.
AU - King, Nicole
AU - Chen, Qian
AU - Xu, Wei
AU - Strauss, John
AU - Breen, Gerome
AU - Lewis, Cathryn M.
AU - Farmer, Anne E.
AU - McGuffin, Peter
AU - Knight, Jo
AU - Vincent, John B.
AU - Kennedy, James L.
N1 - Copyright © 2015 Elsevier Ltd. All rights reserved.
PY - 2015/6
Y1 - 2015/6
N2 - 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.
AB - 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.
KW - Bipolar Disorder
KW - Canada
KW - Chromosomes, Human, Pair 10
KW - Chromosomes, Human, Pair 8
KW - Female
KW - Genetic Association Studies
KW - Genetic Predisposition to Disease
KW - Genotype
KW - Humans
KW - Male
KW - Meta-Analysis as Topic
KW - Oligonucleotide Array Sequence Analysis
KW - Polymorphism, Single Nucleotide
KW - Suicide
U2 - 10.1016/j.jpsychires.2014.11.002
DO - 10.1016/j.jpsychires.2014.11.002
M3 - Journal article
C2 - 25917933
VL - 65
SP - 23
EP - 29
JO - Journal of Psychiatric Research
JF - Journal of Psychiatric Research
SN - 0022-3956
ER -