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  Genome-wide association and meta-analysis of bipolar disorder in individuals of European ancestry

Scott, L. J., Muglia, P., Kong, X. Q., Guan, W., Flickinger, M., Upmanyu, R., et al. (2009). Genome-wide association and meta-analysis of bipolar disorder in individuals of European ancestry. Proceedings of the National Academy of Sciences of the United States of America, 106(18), 7501-7506. doi:10.1073/pnas.0813386106.

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 Urheber:
Scott, Laura J., Autor
Muglia, Pierandrea, Autor
Kong, Xiangyang Q., Autor
Guan, Weihua, Autor
Flickinger, Matthew, Autor
Upmanyu, Ruchi, Autor
Tozzi, Federica, Autor
Li, Jun Z., Autor
Burmeister, Margit, Autor
Absher, Devin, Autor
Thompson, Robert C., Autor
Francks, Clyde1, Autor           
Meng, Fan, Autor
Antoniades, Athos, Autor
Southwick, Audrey M., Autor
Schatzberg, Alan F., Autor
Bunney, William E., Autor
Barchas, Jack D., Autor
Jones, Edward G., Autor
Day, Richard, Autor
Matthews, Keith, AutorMcGuffin, Peter, AutorStrauss, John S., AutorKennedy, James L., AutorMiddleton, Lefkos, AutorRoses, Allen D., AutorWatson, Stanley J., AutorVincent, John B., AutorMyers, Richard M., AutorFarmer, Ann E., AutorAkil, Huda, AutorBurns, Daniel K., AutorBoehnke, Michael, Autor mehr..
Affiliations:
1Genetics Division, Drug Discovery, GlaxoSmithKline Research and Development, Verona, Italy, ou_persistent22              

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 Zusammenfassung: Bipolar disorder (BP) is a disabling and often life-threatening disorder that affects approximately 1% of the population worldwide. To identify genetic variants that increase the risk of BP, we genotyped on the Illumina HumanHap550 Beadchip 2,076 bipolar cases and 1,676 controls of European ancestry from the National Institute of Mental Health Human Genetics Initiative Repository, and the Prechter Repository and samples collected in London, Toronto, and Dundee. We imputed SNP genotypes and tested for SNP-BP association in each sample and then performed meta-analysis across samples. The strongest association P value for this 2-study meta-analysis was 2.4 x 10(-6). We next imputed SNP genotypes and tested for SNP-BP association based on the publicly available Affymetrix 500K genotype data from the Wellcome Trust Case Control Consortium for 1,868 BP cases and a reference set of 12,831 individuals. A 3-study meta-analysis of 3,683 nonoverlapping cases and 14,507 extended controls on >2.3 M genotyped and imputed SNPs resulted in 3 chromosomal regions with association P approximately 10(-7): 1p31.1 (no known genes), 3p21 (>25 known genes), and 5q15 (MCTP1). The most strongly associated nonsynonymous SNP rs1042779 (OR = 1.19, P = 1.8 x 10(-7)) is in the ITIH1 gene on chromosome 3, with other strongly associated nonsynonymous SNPs in GNL3, NEK4, and ITIH3. Thus, these chromosomal regions harbor genes implicated in cell cycle, neurogenesis, neuroplasticity, and neurosignaling. In addition, we replicated the reported ANK3 association results for SNP rs10994336 in the nonoverlapping GSK sample (OR = 1.37, P = 0.042). Although these results are promising, analysis of additional samples will be required to confirm that variant(s) in these regions influence BP risk.

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Sprache(n): eng - English
 Datum: 2009
 Publikationsstatus: Erschienen
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: PMID: 19416921
DOI: 10.1073/pnas.0813386106
 Art des Abschluß: -

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Titel: Proceedings of the National Academy of Sciences of the United States of America
  Andere : Proc. Natl. Acad. Sci. U. S. A.
Genre der Quelle: Zeitschrift
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Affiliations:
Ort, Verlag, Ausgabe: National Academy of Sciences
Seiten: - Band / Heft: 106 (18) Artikelnummer: - Start- / Endseite: 7501 - 7506 Identifikator: Anderer: undefined
Anderer: 0027-8424
CoNE: https://pure.mpg.de/cone/journals/resource/954925427230