Genome-Wide association of bipolar disorder suggests an enrichment of replicable associations in regions near genes

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 Edenberg, Tatiana Foroud, Elliot S. Gershon, Tiffany A. Greenwood, Yiran Guo, Maria Hipolito, Brendan J. Keating, William B. Lawson, Chunyu LiuPamela B. Mahon, Melvin G. McInnis, Francis J. McMahon, Rebecca McKinney, Sarah S. Murray, Caroline M. Nievergelt, John 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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Article numbere1002134
JournalPLoS Genetics
Volume7
Issue number6
DOIs
StatePublished - Jun 2011

Fingerprint

Bipolar Disorder
exons
genome
Genome-Wide Association Study
Genome
Single Nucleotide Polymorphism
gene
Exons
genetic disorders
meta-analysis
Genes
genes
genetic variation
loci
Meta-Analysis
genotype
Genotype
sampling
genome-wide association study
Power (Psychology)

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Smith, E. N., Koller, D. L., Panganiban, C., Szelinger, S., Zhang, P., Badner, J. A., ... Kelsoe, J. R. (2011). Genome-Wide association of bipolar disorder suggests an enrichment of replicable associations in regions near genes. PLoS Genetics, 7(6), [e1002134]. https://doi.org/10.1371/journal.pgen.1002134

Genome-Wide association of bipolar disorder suggests an enrichment of replicable associations in regions near genes. / Smith, Erin N.; Koller, Daniel L.; Panganiban, Corrie; Szelinger, Szabolcs; Zhang, Peng; Badner, Judith A.; Barrett, Thomas B.; Berrettini, Wade H.; Bloss, Cinnamon S.; Byerley, William; Coryell, William; Edenberg, Howard; Foroud, Tatiana; Gershon, Elliot S.; Greenwood, Tiffany A.; Guo, Yiran; Hipolito, Maria; Keating, Brendan J.; Lawson, William B.; Liu, Chunyu; Mahon, Pamela B.; McInnis, Melvin G.; McMahon, Francis J.; McKinney, Rebecca; Murray, Sarah S.; Nievergelt, Caroline M.; Nurnberger, John; Nwulia, Evaristus A.; Potash, James B.; Rice, John; Schulze, Thomas G.; Scheftner, William A.; Shilling, Paul D.; Zandi, Peter P.; Zöllner, Sebastian; Craig, David W.; Schork, Nicholas J.; Kelsoe, John R.

In: PLoS Genetics, Vol. 7, No. 6, e1002134, 06.2011.

Research output: Contribution to journalArticle

Smith, EN, Koller, DL, Panganiban, C, Szelinger, S, Zhang, P, Badner, JA, Barrett, TB, Berrettini, WH, Bloss, CS, Byerley, W, Coryell, W, Edenberg, H, Foroud, T, Gershon, ES, Greenwood, TA, Guo, Y, Hipolito, M, Keating, BJ, Lawson, WB, Liu, C, Mahon, PB, McInnis, MG, McMahon, FJ, McKinney, R, Murray, SS, Nievergelt, CM, Nurnberger, J, Nwulia, EA, Potash, JB, Rice, J, Schulze, TG, Scheftner, WA, Shilling, PD, Zandi, PP, Zöllner, S, Craig, DW, Schork, NJ & Kelsoe, JR 2011, 'Genome-Wide association of bipolar disorder suggests an enrichment of replicable associations in regions near genes', PLoS Genetics, vol. 7, no. 6, e1002134. https://doi.org/10.1371/journal.pgen.1002134
Smith, Erin N. ; Koller, Daniel L. ; Panganiban, Corrie ; Szelinger, Szabolcs ; Zhang, Peng ; Badner, Judith A. ; Barrett, Thomas B. ; Berrettini, Wade H. ; Bloss, Cinnamon S. ; Byerley, William ; Coryell, William ; Edenberg, Howard ; Foroud, Tatiana ; Gershon, Elliot S. ; Greenwood, Tiffany A. ; Guo, Yiran ; Hipolito, Maria ; Keating, Brendan J. ; Lawson, William B. ; Liu, Chunyu ; Mahon, Pamela B. ; McInnis, Melvin G. ; McMahon, Francis J. ; McKinney, Rebecca ; Murray, Sarah S. ; Nievergelt, Caroline M. ; Nurnberger, John ; Nwulia, Evaristus A. ; Potash, James B. ; Rice, John ; Schulze, Thomas G. ; Scheftner, William A. ; Shilling, Paul D. ; Zandi, Peter P. ; Zöllner, Sebastian ; Craig, David W. ; Schork, Nicholas J. ; Kelsoe, John R. / Genome-Wide association of bipolar disorder suggests an enrichment of replicable associations in regions near genes. In: PLoS Genetics. 2011 ; Vol. 7, No. 6.
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abstract = "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.",
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AU - Smith, Erin N.

AU - Koller, Daniel L.

AU - Panganiban, Corrie

AU - Szelinger, Szabolcs

AU - Zhang, Peng

AU - Badner, Judith A.

AU - Barrett, Thomas B.

AU - Berrettini, Wade H.

AU - Bloss, Cinnamon S.

AU - Byerley, William

AU - Coryell, William

AU - Edenberg, Howard

AU - Foroud, Tatiana

AU - Gershon, Elliot S.

AU - Greenwood, Tiffany A.

AU - Guo, Yiran

AU - Hipolito, Maria

AU - Keating, Brendan J.

AU - Lawson, William B.

AU - Liu, Chunyu

AU - Mahon, Pamela B.

AU - McInnis, Melvin G.

AU - McMahon, Francis J.

AU - McKinney, Rebecca

AU - Murray, Sarah S.

AU - Nievergelt, Caroline M.

AU - Nurnberger, John

AU - Nwulia, Evaristus A.

AU - Potash, James B.

AU - Rice, John

AU - Schulze, Thomas G.

AU - Scheftner, William A.

AU - Shilling, Paul D.

AU - Zandi, Peter P.

AU - Zöllner, Sebastian

AU - Craig, David W.

AU - Schork, Nicholas J.

AU - Kelsoe, John R.

PY - 2011/6

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