Genome-Wide Association Study of Irritable vs. Elated Mania Suggests Genetic Differences between Clinical Subtypes of Bipolar Disorder

Tiffany A. Greenwood, John R. Kelsoe, John R. Kelsoe, Tiffany A. Greenwood, Caroline M. Nievergelt, Rebecca McKinney, Paul D. Shilling, Erin N. Smith, Nicholas J. Schork, Cinnamon S. Bloss, John I. Nurnberger, Howard J. Edenberg, Tatiana Foroud, Daniel L. Koller, Elliot S. Gershon, Chunyu Liu, Judith A. Badner, William A. Scheftner, William B. Lawson, Evaristus A. NwuliaMaria Hipolito, William Coryell, James B. Potash, John Rice, William Byerley, Francis J. McMahon, John Nurnberger, Howard Edenberg, Tatiana Foroud, Pamela B. Mahon, Melvin G. McInnis, Sebastian Zöllner, Peng Zhang, David W. Craig, Szabolcs Szelinger, Thomas B. Barrett

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The use of clinical features to define subtypes of a disorder may aid in gene identification for complex diseases. In particular, clinical subtypes of mania may distinguish phenotypic subgroups of bipolar subjects that may also differ genetically. To assess this possibility, we performed a genome-wide association study using genotype data from the Bipolar Genome Study (BiGS) and subjects that were categorized as having either irritable or elated mania during their most severe episode. A bipolar case-only analysis in the GAIN bipolar sample identified several genomic regions that differed between irritable and elated subjects, the most significant of which was for 33 SNPs on chromosome 13q31 (peak p = 2×10-7). This broad peak is in a relative gene desert over an unknown EST and between the SLITRK1 and SLITRK6 genes. Evidence for association to this region came predominantly from subjects in the sample that were originally collected as part of a family-based bipolar linkage study, rather than those collected as bipolar singletons. We then genotyped an additional sample of bipolar singleton cases and controls, and the analysis of irritable vs. elated mania in this new sample did not replicate our previous findings. However, this lack of replication is likely due to the presence of significant differences in terms of clinical co-morbity that were identified between these singleton bipolar cases and those that were selected from families segregating the disorder. Despite these clinical differences, analysis of the combined sample provided continued support for 13q31 and other regions from our initial analysis. Though genome-wide significance was not achieved, our results suggest that irritable mania results from a distinct set of genes, including a region on chromosome 13q31.

Original languageEnglish
Article numbere53804
JournalPLoS One
Volume8
Issue number1
DOIs
StatePublished - Jan 17 2013

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Genome-Wide Association Study
Bipolar Disorder
Genes
Chromosomes
Genome
sampling
genes
Expressed Sequence Tags
chromosomes
genome
Single Nucleotide Polymorphism
Genotype
linkage (genetics)
deserts
genome-wide association study
genomics
genotype

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Greenwood, T. A., Kelsoe, J. R., Kelsoe, J. R., Greenwood, T. A., Nievergelt, C. M., McKinney, R., ... Barrett, T. B. (2013). Genome-Wide Association Study of Irritable vs. Elated Mania Suggests Genetic Differences between Clinical Subtypes of Bipolar Disorder. PLoS One, 8(1), [e53804]. https://doi.org/10.1371/journal.pone.0053804

Genome-Wide Association Study of Irritable vs. Elated Mania Suggests Genetic Differences between Clinical Subtypes of Bipolar Disorder. / Greenwood, Tiffany A.; Kelsoe, John R.; Kelsoe, John R.; Greenwood, Tiffany A.; Nievergelt, Caroline M.; McKinney, Rebecca; Shilling, Paul D.; Smith, Erin N.; Schork, Nicholas J.; Bloss, Cinnamon S.; Nurnberger, John I.; Edenberg, Howard J.; Foroud, Tatiana; Koller, Daniel L.; Gershon, Elliot S.; Liu, Chunyu; Badner, Judith A.; Scheftner, William A.; Lawson, William B.; Nwulia, Evaristus A.; Hipolito, Maria; Coryell, William; Potash, James B.; Rice, John; Byerley, William; McMahon, Francis J.; Nurnberger, John; Edenberg, Howard; Foroud, Tatiana; Mahon, Pamela B.; McInnis, Melvin G.; Zöllner, Sebastian; Zhang, Peng; Craig, David W.; Szelinger, Szabolcs; Barrett, Thomas B.

In: PLoS One, Vol. 8, No. 1, e53804, 17.01.2013.

Research output: Contribution to journalArticle

Greenwood, TA, Kelsoe, JR, Kelsoe, JR, Greenwood, TA, Nievergelt, CM, McKinney, R, Shilling, PD, Smith, EN, Schork, NJ, Bloss, CS, Nurnberger, JI, Edenberg, HJ, Foroud, T, Koller, DL, Gershon, ES, Liu, C, Badner, JA, Scheftner, WA, Lawson, WB, Nwulia, EA, Hipolito, M, Coryell, W, Potash, JB, Rice, J, Byerley, W, McMahon, FJ, Nurnberger, J, Edenberg, H, Foroud, T, Mahon, PB, McInnis, MG, Zöllner, S, Zhang, P, Craig, DW, Szelinger, S & Barrett, TB 2013, 'Genome-Wide Association Study of Irritable vs. Elated Mania Suggests Genetic Differences between Clinical Subtypes of Bipolar Disorder', PLoS One, vol. 8, no. 1, e53804. https://doi.org/10.1371/journal.pone.0053804
Greenwood, Tiffany A. ; Kelsoe, John R. ; Kelsoe, John R. ; Greenwood, Tiffany A. ; Nievergelt, Caroline M. ; McKinney, Rebecca ; Shilling, Paul D. ; Smith, Erin N. ; Schork, Nicholas J. ; Bloss, Cinnamon S. ; Nurnberger, John I. ; Edenberg, Howard J. ; Foroud, Tatiana ; Koller, Daniel L. ; Gershon, Elliot S. ; Liu, Chunyu ; Badner, Judith A. ; Scheftner, William A. ; Lawson, William B. ; Nwulia, Evaristus A. ; Hipolito, Maria ; Coryell, William ; Potash, James B. ; Rice, John ; Byerley, William ; McMahon, Francis J. ; Nurnberger, John ; Edenberg, Howard ; Foroud, Tatiana ; Mahon, Pamela B. ; McInnis, Melvin G. ; Zöllner, Sebastian ; Zhang, Peng ; Craig, David W. ; Szelinger, Szabolcs ; Barrett, Thomas B. / Genome-Wide Association Study of Irritable vs. Elated Mania Suggests Genetic Differences between Clinical Subtypes of Bipolar Disorder. In: PLoS One. 2013 ; Vol. 8, No. 1.
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AU - Kelsoe, John R.

AU - Kelsoe, John R.

AU - Greenwood, Tiffany A.

AU - Nievergelt, Caroline M.

AU - McKinney, Rebecca

AU - Shilling, Paul D.

AU - Smith, Erin N.

AU - Schork, Nicholas J.

AU - Bloss, Cinnamon S.

AU - Nurnberger, John I.

AU - Edenberg, Howard J.

AU - Foroud, Tatiana

AU - Koller, Daniel L.

AU - Gershon, Elliot S.

AU - Liu, Chunyu

AU - Badner, Judith A.

AU - Scheftner, William A.

AU - Lawson, William B.

AU - Nwulia, Evaristus A.

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AU - Coryell, William

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AU - Rice, John

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AU - Edenberg, Howard

AU - Foroud, Tatiana

AU - Mahon, Pamela B.

AU - McInnis, Melvin G.

AU - Zöllner, Sebastian

AU - Zhang, Peng

AU - Craig, David W.

AU - Szelinger, Szabolcs

AU - Barrett, Thomas B.

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