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 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

doi:10.1371/journal.pgen.1002134

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 J. 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 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

School of Medicine

Research output: Contribution to journal › Article › peer-review

53 Scopus citations

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 language	English (US)
Article number	e1002134
Journal	PLoS genetics
Volume	7
Issue number	6
DOIs	https://doi.org/10.1371/journal.pgen.1002134
State	Published - Jun 2011

ASJC Scopus subject areas

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

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Smith, E. N., Koller, D. L., Panganiban, C., Szelinger, S., Zhang, P., Badner, J. A., Barrett, T. B., Berrettini, W. H., Bloss, C. S., Byerley, W., Coryell, W., Edenberg, H. J., Foroud, T., Gershon, E. S., Greenwood, T. A., Guo, Y., Hipolito, M., Keating, B. J., Lawson, W. B., ... Kelsoe, J. R. (2011). Genome-Wide association of bipolar disorder suggests an enrichment of replicable associations in regions near genes. PLoS genetics, 7(6), Article e1002134. https://doi.org/10.1371/journal.pgen.1002134

Smith, EN, Koller, DL, Panganiban, C, Szelinger, S, Zhang, P, Badner, JA, Barrett, TB, Berrettini, WH, Bloss, CS, Byerley, W, Coryell, W, Edenberg, HJ, 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, JI, 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

@article{67eb8aab5c0549abb26ce625e18b7534,

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

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.",

author = "Smith, {Erin N.} and Koller, {Daniel L.} and Corrie Panganiban and Szabolcs Szelinger and Peng Zhang and Badner, {Judith A.} and Barrett, {Thomas B.} and Berrettini, {Wade H.} and Bloss, {Cinnamon S.} and William Byerley and William Coryell and Edenberg, {Howard J.} and Tatiana Foroud and Gershon, {Elliot S.} and Greenwood, {Tiffany A.} and Yiran Guo and Maria Hipolito and Keating, {Brendan J.} and Lawson, {William B.} and Chunyu Liu and Mahon, {Pamela B.} and McInnis, {Melvin G.} and McMahon, {Francis J.} and Rebecca McKinney and Murray, {Sarah S.} and Nievergelt, {Caroline M.} and Nurnberger, {John I.} and Nwulia, {Evaristus A.} and Potash, {James B.} and John Rice and Schulze, {Thomas G.} and Scheftner, {William A.} and Shilling, {Paul D.} and Zandi, {Peter P.} and Sebastian Z{\"o}llner and Craig, {David W.} and Schork, {Nicholas J.} and Kelsoe, {John R.}",

year = "2011",

month = jun,

doi = "10.1371/journal.pgen.1002134",

language = "English (US)",

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T1 - Genome-Wide association of bipolar disorder suggests an enrichment of replicable associations in regions near genes

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 J.

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 I.

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

Y1 - 2011/6

N2 - 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.

AB - 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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M1 - e1002134

ER -

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

Abstract

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