Rights statement: © 2014 Xu et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Genome-wide association study of bipolar disorder in Canadian and UK populations corroborates disease loci including SYNE1 and CSMD1
AU - Xu, Wei
AU - Cohen-Woods, Sarah
AU - Chen, Qian
AU - Noor, Abdul
AU - Knight, Jo
AU - Hosang, Georgina
AU - Parikh, Sagar V.
AU - De Luca, Vincenzo
AU - Tozzi, Federica
AU - Muglia, Pierandrea
AU - Forte, Julia
AU - McQuillin, Andrew
AU - Hu, Pingzhao
AU - Gurling, Hugh M. D.
AU - Kennedy, James L.
AU - McGuffin, Peter
AU - Farmer, Anne
AU - Strauss, John
AU - Vincent, John B.
N1 - © 2014 Xu et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
PY - 2014/1/4
Y1 - 2014/1/4
N2 - BACKGROUND: Recently, genome-wide association studies (GWAS) for cases versus controls using single nucleotide polymorphism microarray data have shown promising findings for complex neuropsychiatric disorders, including bipolar disorder (BD).METHODS: Here we describe a comprehensive genome-wide study of bipolar disorder (BD), cross-referencing analysis from a family-based study of 229 small families with association analysis from over 950 cases and 950 ethnicity-matched controls from the UK and Canada. Further, loci identified in these analyses were supported by pathways identified through pathway analysis on the samples.RESULTS: Although no genome-wide significant markers were identified, the combined GWAS findings have pointed to several genes of interest that support GWAS findings for BD from other groups or consortia, such as at SYNE1 on 6q25, PPP2R2C on 4p16.1, ZNF659 on 3p24.3, CNTNAP5 (2q14.3), and CDH13 (16q23.3). This apparent corroboration across multiple sites gives much confidence to the likelihood of genetic involvement in BD at these loci. In particular, our two-stage strategy found association in both our combined case/control analysis and the family-based analysis on 1q21.2 (closest gene: sphingosine-1-phosphate receptor 1 gene, S1PR1) and on 1q24.1 near the gene TMCO1, and at CSMD1 on 8p23.2, supporting several previous GWAS reports for BD and for schizophrenia. Pathway analysis suggests association of pathways involved in calcium signalling, neuropathic pain signalling, CREB signalling in neurons, glutamate receptor signalling and axonal guidance signalling.CONCLUSIONS: The findings presented here show support for a number of genes previously implicated genes in the etiology of BD, including CSMD1 and SYNE1, as well as evidence for previously unreported genes such as the brain-expressed genes ADCY2, NCALD, WDR60, SCN7A and SPAG16.
AB - BACKGROUND: Recently, genome-wide association studies (GWAS) for cases versus controls using single nucleotide polymorphism microarray data have shown promising findings for complex neuropsychiatric disorders, including bipolar disorder (BD).METHODS: Here we describe a comprehensive genome-wide study of bipolar disorder (BD), cross-referencing analysis from a family-based study of 229 small families with association analysis from over 950 cases and 950 ethnicity-matched controls from the UK and Canada. Further, loci identified in these analyses were supported by pathways identified through pathway analysis on the samples.RESULTS: Although no genome-wide significant markers were identified, the combined GWAS findings have pointed to several genes of interest that support GWAS findings for BD from other groups or consortia, such as at SYNE1 on 6q25, PPP2R2C on 4p16.1, ZNF659 on 3p24.3, CNTNAP5 (2q14.3), and CDH13 (16q23.3). This apparent corroboration across multiple sites gives much confidence to the likelihood of genetic involvement in BD at these loci. In particular, our two-stage strategy found association in both our combined case/control analysis and the family-based analysis on 1q21.2 (closest gene: sphingosine-1-phosphate receptor 1 gene, S1PR1) and on 1q24.1 near the gene TMCO1, and at CSMD1 on 8p23.2, supporting several previous GWAS reports for BD and for schizophrenia. Pathway analysis suggests association of pathways involved in calcium signalling, neuropathic pain signalling, CREB signalling in neurons, glutamate receptor signalling and axonal guidance signalling.CONCLUSIONS: The findings presented here show support for a number of genes previously implicated genes in the etiology of BD, including CSMD1 and SYNE1, as well as evidence for previously unreported genes such as the brain-expressed genes ADCY2, NCALD, WDR60, SCN7A and SPAG16.
KW - Bipolar Disorder
KW - Canada
KW - Cohort Studies
KW - Genetic Loci
KW - Genome-Wide Association Study
KW - Genotype
KW - Great Britain
KW - Humans
KW - Membrane Proteins
KW - Nerve Tissue Proteins
KW - Nuclear Proteins
KW - Pedigree
KW - Reproducibility of Results
KW - Young Adult
U2 - 10.1186/1471-2350-15-2
DO - 10.1186/1471-2350-15-2
M3 - Journal article
C2 - 24387768
VL - 15
JO - Journal of Medical Genetics
JF - Journal of Medical Genetics
SN - 0022-2593
M1 - 2
ER -