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Genome-wide association analysis of age at onset and psychotic symptoms in bipolar disorder

Belmonte Mahon, Pamela, Pirooznia, Mehdi, Goes, Fernando S., Seifuddin, Fayaz, Steele, Jo, Lee, Phil Hyoun, Huang, Jie, Hamshere, Marian Lindsay, DePaulo, J. Raymond, Kelsoe, John R., Rietschel, Marcella, Nöthen, Markus, Cichon, Sven, Gurling, Hugh, Purcell, Shaun, Smoller, Jordan W., Craddock, Nicholas John, Schulze, Thomas G., McMahon, Francis J., Potash, James B. and Zandi, Peter P. 2011. Genome-wide association analysis of age at onset and psychotic symptoms in bipolar disorder. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 156 (3) , pp. 370-378. 10.1002/ajmg.b.31172

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Abstract

Genome-wide association studies (GWAS) have identified several susceptibility loci for bipolar disorder (BP), most notably ANK3. However, most of the inherited risk for BP remains unexplained. One reason for the limited success may be the genetic heterogeneity of BP. Clinical sub-phenotypes of BP may identify more etiologically homogeneous subsets of patients, which can be studied with increased power to detect genetic variation. Here, we report on a mega-analysis of two widely studied sub-phenotypes of BP, age at onset and psychotic symptoms, which are familial and clinically significant. We combined data from three GWAS: NIMH Bipolar Disorder Genetic Association Information Network (GAIN-BP), NIMH Bipolar Disorder Genome Study (BiGS), and a German sample. The combined sample consisted of 2,836 BP cases with information on sub-phenotypes and 2,744 controls. Imputation was performed, resulting in 2.3 million SNPs available for analysis. No SNP reached genome-wide significance for either sub-phenotype. In addition, no SNP reached genome-wide significance in a meta-analysis with an independent replication sample. We had 80% power to detect associations with a common SNP at an OR of 1.6 for psychotic symptoms and a mean difference of 1.8 years in age at onset. Age at onset and psychotic symptoms in BP may be influenced by many genes of smaller effect sizes or other variants not measured well by SNP arrays, such as rare alleles.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher: Wiley-Blackwell
ISSN: 1552-4841
Last Modified: 04 Jun 2017 03:30
URI: http://orca-mwe.cf.ac.uk/id/eprint/22171

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