Genome-wide association study of irritable vs. elated mania suggests genetic differences between clinical subtypes of bipolar disorder.

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-wi...

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Autores principales:	Tiffany A Greenwood, Bipolar Genome Study (BiGS) Consortium, John R Kelsoe
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b7f35ecebc6b4ffab8b63547d7cabb34
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spelling	oai:doaj.org-article:b7f35ecebc6b4ffab8b63547d7cabb342021-11-18T08:01:56ZGenome-wide association study of irritable vs. elated mania suggests genetic differences between clinical subtypes of bipolar disorder.1932-620310.1371/journal.pone.0053804https://doaj.org/article/b7f35ecebc6b4ffab8b63547d7cabb342013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23326512/?tool=EBIhttps://doaj.org/toc/1932-6203The 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.Tiffany A GreenwoodBipolar Genome Study (BiGS) ConsortiumJohn R KelsoePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e53804 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tiffany A Greenwood Bipolar Genome Study (BiGS) Consortium John R Kelsoe Genome-wide association study of irritable vs. elated mania suggests genetic differences between clinical subtypes of bipolar disorder.
description	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.
format	article
author	Tiffany A Greenwood Bipolar Genome Study (BiGS) Consortium John R Kelsoe
author_facet	Tiffany A Greenwood Bipolar Genome Study (BiGS) Consortium John R Kelsoe
author_sort	Tiffany A Greenwood
title	Genome-wide association study of irritable vs. elated mania suggests genetic differences between clinical subtypes of bipolar disorder.
title_short	Genome-wide association study of irritable vs. elated mania suggests genetic differences between clinical subtypes of bipolar disorder.
title_full	Genome-wide association study of irritable vs. elated mania suggests genetic differences between clinical subtypes of bipolar disorder.
title_fullStr	Genome-wide association study of irritable vs. elated mania suggests genetic differences between clinical subtypes of bipolar disorder.
title_full_unstemmed	Genome-wide association study of irritable vs. elated mania suggests genetic differences between clinical subtypes of bipolar disorder.
title_sort	genome-wide association study of irritable vs. elated mania suggests genetic differences between clinical subtypes of bipolar disorder.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/b7f35ecebc6b4ffab8b63547d7cabb34
work_keys_str_mv	AT tiffanyagreenwood genomewideassociationstudyofirritablevselatedmaniasuggestsgeneticdifferencesbetweenclinicalsubtypesofbipolardisorder AT bipolargenomestudybigsconsortium genomewideassociationstudyofirritablevselatedmaniasuggestsgeneticdifferencesbetweenclinicalsubtypesofbipolardisorder AT johnrkelsoe genomewideassociationstudyofirritablevselatedmaniasuggestsgeneticdifferencesbetweenclinicalsubtypesofbipolardisorder
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Genome-wide association study of irritable vs. elated mania suggests genetic differences between clinical subtypes of bipolar disorder.

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