Analysis of the Influence of microRNAs in Lithium Response in Bipolar Disorder.

Authors:
Céline S Reinbold Andreas J Forstner Julian Hecker Janice M Fullerton Per Hoffmann Liping Hou Urs Heilbronner Franziska Degenhardt Mazda Adli Kazufumi Akiyama Nirmala Akula Raffaella Ardau Bárbara Arias Lena Backlund Antonio Benabarre Susanne Bengesser Abesh K Bhattacharjee Joanna M Biernacka Armin Birner Cynthia Marie-Claire Pablo Cervantes Guo-Bo Chen Hsi-Chung Chen Caterina Chillotti Scott R Clark Francesc Colom David A Cousins Cristiana Cruceanu Piotr M Czerski Alexandre Dayer Bruno Étain Peter Falkai Louise Frisén Sébastien Gard Julie S Garnham Fernando S Goes Paul Grof Oliver Gruber Ryota Hashimoto Joanna Hauser Stefan Herms Stéphane Jamain Esther Jiménez Jean-Pierre Kahn Layla Kassem Sarah Kittel-Schneider Sebastian Kliwicki Barbara König Ichiro Kusumi Nina Lackner Gonzalo Laje Mikael Landén Catharina Lavebratt Marion Leboyer Susan G Leckband Carlos A López Jaramillo Glenda MacQueen Mirko Manchia Lina Martinsson Manuel Mattheisen Michael J McCarthy Susan L McElroy Marina Mitjans Francis M Mondimore Palmiero Monteleone Caroline M Nievergelt Urban Ösby Norio Ozaki Roy H Perlis Andrea Pfennig Daniela Reich-Erkelenz Guy A Rouleau Peter R Schofield K Oliver Schubert Barbara W Schweizer Florian Seemüller Giovanni Severino Tatyana Shekhtman Paul D Shilling Kazutaka Shimoda Christian Simhandl Claire M Slaney Jordan W Smoller Alessio Squassina Thomas J Stamm Pavla Stopkova Sarah K Tighe Alfonso Tortorella Gustavo Turecki Julia Volkert Stephanie H Witt Adam J Wright L Trevor Young Peter P Zandi James B Potash J Raymond DePaulo Michael Bauer Eva Reininghaus Tomáš Novák Jean-Michel Aubry Mario Maj Bernhard T Baune Philip B Mitchell Eduard Vieta Mark A Frye Janusz K Rybakowski Po-Hsiu Kuo Tadafumi Kato Maria Grigoroiu-Serbanescu Andreas Reif Maria Del Zompo Frank Bellivier Martin Schalling Naomi R Wray John R Kelsoe Martin Alda Francis J McMahon Thomas G Schulze Marcella Rietschel Markus M Nöthen Sven Cichon

Front Psychiatry 2018 31;9:207. Epub 2018 May 31.

Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland.

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 ( = 2,563 patients) using a set-based testing approach adapted from the versatile gene-based test for GWAS (VEGAS2). In the candidate approach, 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 showing the strongest association with the continuous trait ( = 9.80E-04) and with the dichotomous phenotype ( = 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.

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http://dx.doi.org/10.3389/fpsyt.2018.00207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5991073PMC
May 2018
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