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Type: Journal article
Title: Analysis of the influence of microRNAs in Lithium Response in Bipolar Disorder
Author: Reinbold, C.
Clark, S.
Schubert, K.
Baune, B.
Cichon, S.
Citation: Frontiers in Psychiatry, 2018; 9(MAY):207-1-207-9
Publisher: Frontiers Media
Issue Date: 2018
ISSN: 1664-0640
Statement of
Céline S. Reinbold, Andreas J. Forstner, Julian Hecker, Janice M. Fullerton … Scott R. Clark … Klaus O. (Oliver) Schubert … et al.
Abstract: 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.
Keywords: Bipolar disorder, lithium response; microRNA; common variants; genome-wide association study
Rights: © 2018 Reinbold, Forstner, Hecker, Fullerton, Hoffmann, Hou, Heilbronner, Degenhardt, Adli, Akiyama, Akula, Ardau, Arias, Backlund, Benabarre, Bengesser, Bhattacharjee, Biernacka, Birner, Marie-Claire, Cervantes, Chen, Chen, Chillotti, Clark, Colom, Cousins, Cruceanu, Czerski, Dayer, Étain, Falkai, Frisén, Gard, Garnham, Goes, Grof, Gruber, Hashimoto, Hauser, Herms, Jamain, Jiménez, Kahn, Kassem, Kittel-Schneider, Kliwicki, König, Kusumi, Lackner, Laje, Landén, Lavebratt, Leboyer, Leckband, López Jaramillo, MacQueen, Manchia, Martinsson, Mattheisen, McCarthy, McElroy, Mitjans, Mondimore, Monteleone, Nievergelt, Ösby, Ozaki, Perlis, Pfennig, Reich-Erkelenz, Rouleau, Schofield, Schubert, Schweizer, Seemüller, Severino, Shekhtman, Shilling, Shimoda, Simhandl, Slaney, Smoller, Squassina, Stamm, Stopkova, Tighe, Tortorella, Turecki, Volkert, Witt, Wright, Young, Zandi, Potash, DePaulo, Bauer, Reininghaus, Novák, Aubry, Maj, Baune, Mitchell, Vieta, Frye, Rybakowski, Kuo, Kato, Grigoroiu-Serbanescu, Reif, Del Zompo, Bellivier, Schalling, Wray, Kelsoe, Alda, McMahon, Schulze, Rietschel, Nöthen and Cichon. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
RMID: 0030090465
DOI: 10.3389/fpsyt.2018.00207
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Appears in Collections:Psychology publications

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