Showing papers by "L. Trevor Young published in 2018"
University of Basel1, University of Bonn2, Harvard University3, Neuroscience Research Australia4, University of New South Wales5, United States Department of Health and Human Services6, Ludwig Maximilian University of Munich7, Charité8, Dokkyo Medical University9, University of Barcelona10, Karolinska University Hospital11, Medical University of Graz12, Mayo Clinic13, French Institute of Health and Medical Research14, University of Paris15, University of California, San Diego16, McGill University Health Centre17, University of Queensland18, National Taiwan University19, University of Adelaide20, Newcastle University21, Douglas Mental Health University Institute22, Poznan University of Medical Sciences23, Geneva College24, Dalhousie University25, Johns Hopkins University26, University of Göttingen27, Osaka University28, University of Lorraine29, Goethe University Frankfurt30, Hokkaido University31, University of Gothenburg32, Karolinska Institutet33, Veterans Health Administration34, University of Antioquia35, University of Calgary36, University of Cagliari37, Aarhus University38, University of Cincinnati39, University of Salerno40, Seconda Università degli Studi di Napoli41, Nagoya University42, Dresden University of Technology43, Montreal Neurological Institute and Hospital44, University of Iowa45, Heidelberg University46, University of British Columbia47, RIKEN Brain Science Institute48, National Institutes of Health49
TL;DR: In this paper, the authors performed a genome-wide analysis of the involvement of miRNAs in bipolar disorder and identified nine miRNA associated with lithium response in BD and systematically analyzed whether any other miRNA in the genome is implicated in the response to lithium.
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.
28 citations