Genome-wide association of bipolar disorder suggests an enrichment of replicable associations in regions near genes.
Although a highly heritable and disabling disease, bipolar disorder's (BD) genetic variants have been challenging to identify. We present new genotype data for 1,190 cases and 401 controls and perform a genome-wide association study including additional samples for a total of 2,191 cases and 1,...
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2011
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oai:doaj.org-article:3c68f3061e9a495589546577b22507ee2021-11-18T06:17:17ZGenome-wide association of bipolar disorder suggests an enrichment of replicable associations in regions near genes.1553-73901553-740410.1371/journal.pgen.1002134https://doaj.org/article/3c68f3061e9a495589546577b22507ee2011-06-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21738484/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Although a highly heritable and disabling disease, bipolar disorder's (BD) genetic variants have been challenging to identify. We present new genotype data for 1,190 cases and 401 controls and perform a genome-wide association study including additional samples for a total of 2,191 cases and 1,434 controls. We do not detect genome-wide significant associations for individual loci; however, across all SNPs, we show an association between the power to detect effects calculated from a previous genome-wide association study and evidence for replication (P = 1.5×10(-7)). To demonstrate that this result is not likely to be a false positive, we analyze replication rates in a large meta-analysis of height and show that, in a large enough study, associations replicate as a function of power, approaching a linear relationship. Within BD, SNPs near exons exhibit a greater probability of replication, supporting an enrichment of reproducible associations near functional regions of genes. These results indicate that there is likely common genetic variation associated with BD near exons (±10 kb) that could be identified in larger studies and, further, provide a framework for assessing the potential for replication when combining results from multiple studies.Erin N SmithDaniel L KollerCorrie PanganibanSzabolcs SzelingerPeng ZhangJudith A BadnerThomas B BarrettWade H BerrettiniCinnamon S BlossWilliam ByerleyWilliam CoryellHoward J EdenbergTatiana ForoudElliot S GershonTiffany A GreenwoodYiran GuoMaria HipolitoBrendan J KeatingWilliam B LawsonChunyu LiuPamela B MahonMelvin G McInnisFrancis J McMahonRebecca McKinneySarah S MurrayCaroline M NievergeltJohn I NurnbergerEvaristus A NwuliaJames B PotashJohn RiceThomas G SchulzeWilliam A ScheftnerPaul D ShillingPeter P ZandiSebastian ZöllnerDavid W CraigNicholas J SchorkJohn R KelsoePublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 7, Iss 6, p e1002134 (2011) |
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| collection |
DOAJ |
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EN |
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Genetics QH426-470 |
| spellingShingle |
Genetics QH426-470 Erin N Smith Daniel L Koller Corrie Panganiban Szabolcs Szelinger Peng Zhang Judith A Badner Thomas B Barrett Wade H Berrettini Cinnamon S Bloss William Byerley William Coryell Howard J Edenberg Tatiana Foroud Elliot S Gershon Tiffany A Greenwood Yiran Guo Maria Hipolito Brendan J Keating William B Lawson Chunyu Liu Pamela B Mahon Melvin G McInnis Francis J McMahon Rebecca McKinney Sarah S Murray Caroline M Nievergelt John I Nurnberger Evaristus A Nwulia James B Potash John Rice Thomas G Schulze William A Scheftner Paul D Shilling Peter P Zandi Sebastian Zöllner David W Craig Nicholas J Schork John R Kelsoe Genome-wide association of bipolar disorder suggests an enrichment of replicable associations in regions near genes. |
| description |
Although a highly heritable and disabling disease, bipolar disorder's (BD) genetic variants have been challenging to identify. We present new genotype data for 1,190 cases and 401 controls and perform a genome-wide association study including additional samples for a total of 2,191 cases and 1,434 controls. We do not detect genome-wide significant associations for individual loci; however, across all SNPs, we show an association between the power to detect effects calculated from a previous genome-wide association study and evidence for replication (P = 1.5×10(-7)). To demonstrate that this result is not likely to be a false positive, we analyze replication rates in a large meta-analysis of height and show that, in a large enough study, associations replicate as a function of power, approaching a linear relationship. Within BD, SNPs near exons exhibit a greater probability of replication, supporting an enrichment of reproducible associations near functional regions of genes. These results indicate that there is likely common genetic variation associated with BD near exons (±10 kb) that could be identified in larger studies and, further, provide a framework for assessing the potential for replication when combining results from multiple studies. |
| format |
article |
| author |
Erin N Smith Daniel L Koller Corrie Panganiban Szabolcs Szelinger Peng Zhang Judith A Badner Thomas B Barrett Wade H Berrettini Cinnamon S Bloss William Byerley William Coryell Howard J Edenberg Tatiana Foroud Elliot S Gershon Tiffany A Greenwood Yiran Guo Maria Hipolito Brendan J Keating William B Lawson Chunyu Liu Pamela B Mahon Melvin G McInnis Francis J McMahon Rebecca McKinney Sarah S Murray Caroline M Nievergelt John I Nurnberger Evaristus A Nwulia James B Potash John Rice Thomas G Schulze William A Scheftner Paul D Shilling Peter P Zandi Sebastian Zöllner David W Craig Nicholas J Schork John R Kelsoe |
| author_facet |
Erin N Smith Daniel L Koller Corrie Panganiban Szabolcs Szelinger Peng Zhang Judith A Badner Thomas B Barrett Wade H Berrettini Cinnamon S Bloss William Byerley William Coryell Howard J Edenberg Tatiana Foroud Elliot S Gershon Tiffany A Greenwood Yiran Guo Maria Hipolito Brendan J Keating William B Lawson Chunyu Liu Pamela B Mahon Melvin G McInnis Francis J McMahon Rebecca McKinney Sarah S Murray Caroline M Nievergelt John I Nurnberger Evaristus A Nwulia James B Potash John Rice Thomas G Schulze William A Scheftner Paul D Shilling Peter P Zandi Sebastian Zöllner David W Craig Nicholas J Schork John R Kelsoe |
| author_sort |
Erin N Smith |
| title |
Genome-wide association of bipolar disorder suggests an enrichment of replicable associations in regions near genes. |
| title_short |
Genome-wide association of bipolar disorder suggests an enrichment of replicable associations in regions near genes. |
| title_full |
Genome-wide association of bipolar disorder suggests an enrichment of replicable associations in regions near genes. |
| title_fullStr |
Genome-wide association of bipolar disorder suggests an enrichment of replicable associations in regions near genes. |
| title_full_unstemmed |
Genome-wide association of bipolar disorder suggests an enrichment of replicable associations in regions near genes. |
| title_sort |
genome-wide association of bipolar disorder suggests an enrichment of replicable associations in regions near genes. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/3c68f3061e9a495589546577b22507ee |
| work_keys_str_mv |
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