Genome-wide association study of bipolar disorder in Canadian and UK populations corroborates disease loci including SYNE1 and CSMD1

Xu, Wei and Cohen-Woods, Sarah and Chen, Qian and Noor, Abdul and Knight, Jo and Hosang, Georgina and Parikh, Sagar V. and De Luca, Vincenzo and Tozzi, Federica and Muglia, Pierandrea and Forte, Julia and McQuillin, Andrew and Hu, Pingzhao and Gurling, Hugh M. D. and Kennedy, James L. and McGuffin, Peter and Farmer, Anne and Strauss, John and Vincent, John B. (2014) Genome-wide association study of bipolar disorder in Canadian and UK populations corroborates disease loci including SYNE1 and CSMD1. Journal of Medical Genetics, 15: 2. ISSN 0022-2593

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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.

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Journal Article
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Journal of Medical Genetics
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© 2014 Xu et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Uncontrolled Keywords:
?? bipolar disordercanadacohort studiesgenetic locigenome-wide association studygenotypegreat britainhumansmembrane proteinsnerve tissue proteinsnuclear proteinspedigreereproducibility of resultsyoung adultgeneticsgenetics(clinical) ??
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08 Jun 2016 08:12
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26 Jan 2024 01:19