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Am J Med Genet B Neuropsychiatr Genet. 2011 Apr;156B(3):370-8. doi: 10.1002/ajmg.b.31172. Epub 2011 Feb 8.

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

Collaborators (186)

Nurnberger J, Miller M, Bowman E, Reich T, Goate A, Rice J, DePaulo JR Jr, Simpson S, Stine C, Gershon E, Kazuba D, Maxwell E, Nurnberger J, Miller MJ, Bowman ES, Rau L, Moe PR, Samavedy N, El-Mallakh R, Manji H, Glitz DA, Meyer ET, Smiley C, Foroud T, Flury L, Dick DM, Edenberg H, Rice J, Reich T, Goate A, Bierut L, McInnis M, DePaulo JR Jr, MacKinnon DF, Mondimore FM, Potash JB, Zandi PP, Avramopoulos D, Payne J, Berrettini W, Byerley W, Vawter M, Coryell W, Crowe R, Gershon E, Badner J, McMahon F, Liu C, Sanders A, Caserta M, Dinwiddie S, Nguyen T, Harakal D, Kelsoe J, McKinney R, Scheftnerv W, Kravitz HM, Marta D, Vaughn-Brown A, Bederow L, McMahon FJ, Kassem L, Detera-Wadleigh S, Austin L, Murphy DL, Nurnberger J, Miller MJ, Bowman ES, Rau NL, Moe PR, Samavedy N, El-Mallakh R, Manji H, Glitz DA, Meyer ET, Smiley C, Foroud T, Flury L, Dick DM, Edenberg H, Rice J, Reich T, Goate A, Bierut L, McInnis M, DePaulo JR Jr, MacKinnon DF, Mondimore FM, Potash JB, Zandi PP, Avramopoulos D, Payne J, Berrettini W, Byerley W, Vinogradov S, Coryell W, Crowe R, Gershon E, Badner J, McMahon F, Liu C, Sanders A, Caserta M, Dinwiddie S, Nguyen T, Harakal D, Kelsoe J, McKinney R, Scheftner W, Kravitz HM, Marta D, Vaughn-Brown A, Bederow L, McMahon FJ, Kassem L, Detera-Wadleigh S, Austin L, Murphy DL, Lawson WB, Nwulia E, Hipolito M, Gejman PV, Sanders AR, Amin F, Buccola N, Byerley W, Cloninger CR, Crowe R, Black D, Freedman R, Levinson D, Mowry B, Silverman J, Kelsoe JR, Greenwood TA, Shilling PD, Nievergelt C, Schork N, Smith EN, Nurnberger J, Edenberg HJ, Foroud T, Gershon E, Liu C, Badner JA, Scheftner WA, Lawson WB, Nwulia EA, Hipolito M, Coryell W, Rice J, Byerley W, McMahon F, Schulze TG, Berrettini W, Potash JB, Zandi PP, Mahon PB, McInnis MG, Zöllner S, Craig D, Szelinger S, Breen G, Clair DS, Caesar S, Gordon-Smith K, Jones L, Fraser C, Green EK, Grozeva D, Hamshere ML, Holmans PA, Jones IR, Kirov G, Moskvina V, Nikolov I, O'Donovan MC, Owen MJ, Craddock N, Collier DA, Elkin A, Farmer A, Williamson R, McGuffin P, Young AH, Ferrier IN.

Author information

1
Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.

Erratum in

  • Am J Med Genet B Neuropsychiatr Genet. 2011 Sep;156B(6):749-50.

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.

PMID:
21305692
PMCID:
PMC3178836
DOI:
10.1002/ajmg.b.31172
[Indexed for MEDLINE]
Free PMC Article

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