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

@article{citeulike:4493718, abstract = {10.1073/pnas.0813386106 Bipolar disorder (BP) is a disabling and often life-threatening disorder that affects \^{a}‰ˆ1\% 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 value for this 2-study meta-analysis was 2.4 \~{A}— 10. 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 \^{a}‰ˆ 10: 1p31.1 (no known genes), 3p21 (>25 known genes), and 5q15 (). The most strongly associated nonsynonymous SNP rs1042779 (OR = 1.19, = 1.8 \~{A}— 10) is in the gene on chromosome 3, with other strongly associated nonsynonymous SNPs in , , and . Thus, these chromosomal regions harbor genes implicated in cell cycle, neurogenesis, neuroplasticity, and neurosignaling. In addition, we replicated the reported association results for SNP rs10994336 in the nonoverlapping GSK sample (OR = 1.37, = 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.}, author = {Scott, Laura J. and Muglia, Pierandrea and Kong, Xiangyang Q. and Guan, Weihua and Flickinger, Matthew and Upmanyu, Ruchi and Tozzi, Federica and Li, Jun Z. and Burmeister, Margit and Absher, Devin and Thompson, Robert C. and Francks, Clyde and Meng, Fan and Antoniades, Athos and Southwick, Audrey M. and Schatzberg, Alan F. and Bunney, William E. and Barchas, Jack D. and Jones, Edward G. and Day, Richard and Matthews, Keith and McGuffin, Peter and Strauss, John S. and Kennedy, James L. and Middleton, Lefkos and Roses, Allen D. and Watson, Stanley J. and Vincent, John B. and Myers, Richard M. and Farmer, Ann E. and Akil, Huda and Burns, Daniel K. and Boehnke, Michael}, citeulike-article-id = {4493718}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0813386106}, citeulike-linkout-1 = {http://www.pnas.org/content/106/18/7501.abstract}, citeulike-linkout-2 = {http://www.pnas.org/content/106/18/7501.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/19416921}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=19416921}, day = {5}, doi = {10.1073/pnas.0813386106}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, keywords = {bipolar, cns, gwas}, month = {May}, number = {18}, pages = {7501--7506}, posted-at = {2009-05-08 14:31:11}, priority = {2}, title = {Genome-wide association and meta-analysis of bipolar disorder in individuals of European ancestry}, url = {http://dx.doi.org/10.1073/pnas.0813386106}, volume = {106}, year = {2009} }

TY - JOUR ID - citeulike:4493718 L3 - citeulike-article-id:4493718 N2 - 10.1073/pnas.0813386106 Bipolar disorder (BP) is a disabling and often life-threatening disorder that affects ≈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 value for this 2-study meta-analysis was 2.4 × 10. 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 ≈ 10: 1p31.1 (no known genes), 3p21 (>25 known genes), and 5q15 (). The most strongly associated nonsynonymous SNP rs1042779 (OR = 1.19, = 1.8 × 10) is in the gene on chromosome 3, with other strongly associated nonsynonymous SNPs in , , and . Thus, these chromosomal regions harbor genes implicated in cell cycle, neurogenesis, neuroplasticity, and neurosignaling. In addition, we replicated the reported association results for SNP rs10994336 in the nonoverlapping GSK sample (OR = 1.37, = 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. IS - 18 JF - Proceedings of the National Academy of Sciences SN - 1091-6490 EP - 7506 TI - Genome-wide association and meta-analysis of bipolar disorder in individuals of European ancestry VL - 106 SP - 7501 KW - bipolar KW - cns KW - gwas AU - Scott, Laura AU - Muglia, Pierandrea AU - Kong, Xiangyang AU - Guan, Weihua AU - Flickinger, Matthew AU - Upmanyu, Ruchi AU - Tozzi, Federica AU - Li, Jun AU - Burmeister, Margit AU - Absher, Devin AU - Thompson, Robert AU - Francks, Clyde AU - Meng, Fan AU - Antoniades, Athos AU - Southwick, Audrey AU - Schatzberg, Alan AU - Bunney, William AU - Barchas, Jack AU - Jones, Edward AU - Day, Richard AU - Matthews, Keith AU - McGuffin, Peter AU - Strauss, John AU - Kennedy, James AU - Middleton, Lefkos AU - Roses, Allen AU - Watson, Stanley AU - Vincent, John AU - Myers, Richard AU - Farmer, Ann AU - Akil, Huda AU - Burns, Daniel AU - Boehnke, Michael PY - 2009/05/05/ UR - http://dx.doi.org/10.1073/pnas.0813386106 ER -