Analysis of the influence of microRNAs in lithium response in bipolar disorder

Bipolar disorder (BD) is a common, highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. Lithium is the best-established long-term treatment for BD, even though individual response is highly variable Evidence suggests that some of this variability has...

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Authors: Arias Sampériz, Bárbara, Benabarre, Antonio, Vieta i Pascual, Eduard, 1963-
Format: article
Status:Published version
Publication Date:2018
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/139671
Online Access:https://hdl.handle.net/2445/139671
Access Level:Open access
Keyword:Trastorn bipolar
Liti
Manic-depressive illness
Lithium
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spelling Analysis of the influence of microRNAs in lithium response in bipolar disorderArias Sampériz, BárbaraBenabarre, AntonioVieta i Pascual, Eduard, 1963-Trastorn bipolarLitiManic-depressive illnessLithiumBipolar disorder (BD) is a common, highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. Lithium is the best-established long-term treatment for BD, even though individual response is highly variable Evidence suggests that some of this variability has a genetic basis. This is supported by the largest genome-wide association study (GWAS) of lithium response to date conducted by the International Consortium on Lithium Genetics (ConLiGen) Recently, we performed the first genome-wide analysis of the involvement of miRNAs in BD and identified nine BD associated miRNAs However, it is unknown whether these miRNAs are also associated with lithium response in BD. In the present study, we therefore tested whether common variants at these nine candidate miRNAs contribute to the variance in lithium response in BD. Furthermore, we systematically analyzed whether any other miRNA in the genome is implicated in the response to lithium. For this purpose, we performed gene-based tests for all known miRNA coding genes in the ConLiGen GWAS dataset (n = 2,563 patients) using a set-based testing approach adapted from the versatile gene based test for GWAS (VEGAS2). In the candidate approach, miR-499a showed a nominally significant association with lithium response, providing some evidence for involvement in both development and treatment of BD. In the genome-wide miRNA analysis, 71 miRNAs showed nominally significant associations with the dichotomous phenotype and 106 with the continuous trait for treatment response. A total of 15 miRNAs revealed nominal significance in both phenotypes with miR-633 showing the strongest association with the continuous trait (p = 9.80E-04) and miR-607 with the dichotomous phenotype (p = 5.79E-04). No association between miRNAs and treatment response to lithium in BD in either of the tested conditions withstood multiple testing correction. Given the limited power of our study, the investigation of miRNAs in larger GWAS samples of BD and lithium response is warranted.Frontiers Media2019201920182019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion9 p.application/pdfhttps://hdl.handle.net/2445/139671Articles publicats en revistes (Medicina)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.3389/fpsyt.2018.00207Frontiers In Psychiatry, 2018, vol. 9, p. 3389https://doi.org/10.3389/fpsyt.2018.00207cc-by (c) Arias Sampériz, Bárbara et al., 2018http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1396712026-05-29T05:05:01Z
dc.title.none.fl_str_mv Analysis of the influence of microRNAs in lithium response in bipolar disorder
title Analysis of the influence of microRNAs in lithium response in bipolar disorder
spellingShingle Analysis of the influence of microRNAs in lithium response in bipolar disorder
Arias Sampériz, Bárbara
Trastorn bipolar
Liti
Manic-depressive illness
Lithium
title_short Analysis of the influence of microRNAs in lithium response in bipolar disorder
title_full Analysis of the influence of microRNAs in lithium response in bipolar disorder
title_fullStr Analysis of the influence of microRNAs in lithium response in bipolar disorder
title_full_unstemmed Analysis of the influence of microRNAs in lithium response in bipolar disorder
title_sort Analysis of the influence of microRNAs in lithium response in bipolar disorder
dc.creator.none.fl_str_mv Arias Sampériz, Bárbara
Benabarre, Antonio
Vieta i Pascual, Eduard, 1963-
author Arias Sampériz, Bárbara
author_facet Arias Sampériz, Bárbara
Benabarre, Antonio
Vieta i Pascual, Eduard, 1963-
author_role author
author2 Benabarre, Antonio
Vieta i Pascual, Eduard, 1963-
author2_role author
author
dc.subject.none.fl_str_mv Trastorn bipolar
Liti
Manic-depressive illness
Lithium
topic Trastorn bipolar
Liti
Manic-depressive illness
Lithium
description Bipolar disorder (BD) is a common, highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. Lithium is the best-established long-term treatment for BD, even though individual response is highly variable Evidence suggests that some of this variability has a genetic basis. This is supported by the largest genome-wide association study (GWAS) of lithium response to date conducted by the International Consortium on Lithium Genetics (ConLiGen) Recently, we performed the first genome-wide analysis of the involvement of miRNAs in BD and identified nine BD associated miRNAs However, it is unknown whether these miRNAs are also associated with lithium response in BD. In the present study, we therefore tested whether common variants at these nine candidate miRNAs contribute to the variance in lithium response in BD. Furthermore, we systematically analyzed whether any other miRNA in the genome is implicated in the response to lithium. For this purpose, we performed gene-based tests for all known miRNA coding genes in the ConLiGen GWAS dataset (n = 2,563 patients) using a set-based testing approach adapted from the versatile gene based test for GWAS (VEGAS2). In the candidate approach, miR-499a showed a nominally significant association with lithium response, providing some evidence for involvement in both development and treatment of BD. In the genome-wide miRNA analysis, 71 miRNAs showed nominally significant associations with the dichotomous phenotype and 106 with the continuous trait for treatment response. A total of 15 miRNAs revealed nominal significance in both phenotypes with miR-633 showing the strongest association with the continuous trait (p = 9.80E-04) and miR-607 with the dichotomous phenotype (p = 5.79E-04). No association between miRNAs and treatment response to lithium in BD in either of the tested conditions withstood multiple testing correction. Given the limited power of our study, the investigation of miRNAs in larger GWAS samples of BD and lithium response is warranted.
publishDate 2018
dc.date.none.fl_str_mv 2018
2019
2019
2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/139671
url https://hdl.handle.net/2445/139671
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3389/fpsyt.2018.00207
Frontiers In Psychiatry, 2018, vol. 9, p. 3389
https://doi.org/10.3389/fpsyt.2018.00207
dc.rights.none.fl_str_mv cc-by (c) Arias Sampériz, Bárbara et al., 2018
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Arias Sampériz, Bárbara et al., 2018
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 9 p.
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv Articles publicats en revistes (Medicina)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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