Reinbold, C. S., Forstner, A. J., Hecker, J., Fullerton, J. M., Hoffmann, P., Hou, L., Heilbronner, U., Degenhardt, F., Adli, M., Akiyama, K., Akula, N., Ardau, R., Arias, B., Backlund, L., Benabarre, A., Bengesser, S., Bhattacharjee, A. K., Biernacka, J. M., Birner, A., ... Cichon, S. (2018). Analysis of the influence of microRNAs in lithium response in bipolar disorder. Frontiers in Psychiatry, 9(MAY), Article 207. https://doi.org/10.3389/fpsyt.2018.00207
Reinbold, CS, Forstner, AJ, Hecker, J, Fullerton, JM, Hoffmann, P, Hou, L, Heilbronner, U, Degenhardt, F, Adli, M, Akiyama, K, Akula, N, Ardau, R, Arias, B, Backlund, L, Benabarre, A, Bengesser, S, Bhattacharjee, AK, Biernacka, JM, Birner, A, Marie-Claire, C, Cervantes, P, Chen, GB, Chen, HC, Chillotti, C, Clark, SR, Colom, F, Cousins, DA, Cruceanu, C, Czerski, PM, Dayer, A, Étain, B, Falkai, P, Frisén, L, Gard, S, Garnham, JS, Goes, FS, Grof, P, Gruber, O, Hashimoto, R, Hauser, J, Herms, S, Jamain, S, Jiménez, E, Kahn, JP, Kassem, L, Kittel-Schneider, S, Kliwicki, S, König, B, Kusumi, I, Lackner, N, Laje, G, Landén, M, Lavebratt, C, Leboyer, M, Leckband, SG, Jaramillo, CAL, MacQueen, G, Manchia, M, Martinsson, L, Mattheisen, M, McCarthy, MJ, McElroy, SL, Mitjans, M, Mondimore, FM, Monteleone, P, Nievergelt, CM, Ösby, U, Ozaki, N, Perlis, RH, Pfennig, A, Reich-Erkelenz, D, Rouleau, GA, Schofield, PR, Schubert, KO, Schweizer, BW, Seemüller, F, Severino, G, Shekhtman, T, Shilling, PD, Shimoda, K, Simhandl, C, Slaney, CM, Smoller, JW, Squassina, A, Stamm, TJ, Stopkova, P, Tighe, SK, Tortorella, A, Turecki, G, Volkert, J, Witt, SH, Wright, AJ, Trevor Young, L, Zandi, PP, Potash, JB, DePaulo, JR, Bauer, M, Reininghaus, E, Novák, T, Aubry, JM, Maj, M, Baune, BT, Mitchell, PB, Vieta, E, Frye, MA, Rybakowski, JK, Kuo, PH, Kato, T, Grigoroiu-Serbanescu, M, Reif, A, Zompo, MD, Bellivier, F, Schalling, M, Wray, NR, Kelsoe, JR, Alda, M, McMahon, FJ, Schulze, TG, Rietschel, M, Nöthen, MM & Cichon, S 2018, 'Analysis of the influence of microRNAs in lithium response in bipolar disorder', Frontiers in Psychiatry, vol. 9, no. MAY, 207. https://doi.org/10.3389/fpsyt.2018.00207
@article{bf3821274a7247e48712328c8dc58e1d,
title = "Analysis of the influence of microRNAs in lithium response in bipolar disorder",
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.",
author = "Reinbold, {C{\'e}line S.} and Forstner, {Andreas J.} and Julian Hecker and Fullerton, {Janice M.} and Per Hoffmann and Liping Hou and Urs Heilbronner and Franziska Degenhardt and Mazda Adli and Kazufumi Akiyama and Nirmala Akula and Raffaella Ardau and B{\'a}rbara Arias and Lena Backlund and Antonio Benabarre and Susanne Bengesser and Bhattacharjee, {Abesh K.} and Biernacka, {Joanna M.} and Armin Birner and Cynthia Marie-Claire and Pablo Cervantes and Chen, {Guo Bo} and Chen, {Hsi Chung} and Caterina Chillotti and Clark, {Scott R.} and Francesc Colom and Cousins, {David A.} and Cristiana Cruceanu and Czerski, {Piotr M.} and Alexandre Dayer and Bruno {\'E}tain and Peter Falkai and Louise Fris{\'e}n and S{\'e}bastien Gard and Garnham, {Julie S.} and Goes, {Fernando S.} and Paul Grof and Oliver Gruber and Ryota Hashimoto and Joanna Hauser and Stefan Herms and St{\'e}phane Jamain and Esther Jim{\'e}nez and Kahn, {Jean Pierre} and Layla Kassem and Sarah Kittel-Schneider and Sebastian Kliwicki and Barbara K{\"o}nig and Ichiro Kusumi and Nina Lackner and Gonzalo Laje and Mikael Land{\'e}n and Catharina Lavebratt and Marion Leboyer and Leckband, {Susan G.} and Jaramillo, {Carlos A.L{\'o}pez} and Glenda MacQueen and Mirko Manchia and Lina Martinsson and Manuel Mattheisen and McCarthy, {Michael J.} and McElroy, {Susan L.} and Marina Mitjans and Mondimore, {Francis M.} and Palmiero Monteleone and Nievergelt, {Caroline M.} and Urban {\"O}sby and Norio Ozaki and Perlis, {Roy H.} and Andrea Pfennig and Daniela Reich-Erkelenz and Rouleau, {Guy A.} and Schofield, {Peter R.} and Schubert, {K. Oliver} and Schweizer, {Barbara W.} and Florian Seem{\"u}ller and Giovanni Severino and Tatyana Shekhtman and Shilling, {Paul D.} and Kazutaka Shimoda and Christian Simhandl and Slaney, {Claire M.} and Smoller, {Jordan W.} and Alessio Squassina and Stamm, {Thomas J.} and Pavla Stopkova and Tighe, {Sarah K.} and Alfonso Tortorella and Gustavo Turecki and Julia Volkert and Witt, {Stephanie H.} and Wright, {Adam J.} and {Trevor Young}, L. and Zandi, {Peter P.} and Potash, {James B.} and DePaulo, {J. Raymond} and Michael Bauer and Eva Reininghaus and Tom{\'a}{\v s} Nov{\'a}k and Aubry, {Jean Michel} and Mario Maj and Baune, {Bernhard T.} and Mitchell, {Philip B.} and Eduard Vieta and Frye, {Mark A.} and Rybakowski, {Janusz K.} and Kuo, {Po Hsiu} and Tadafumi Kato and Maria Grigoroiu-Serbanescu and Andreas Reif and Zompo, {Maria Del} and Frank Bellivier and Martin Schalling and Wray, {Naomi R.} and Kelsoe, {John R.} and Martin Alda and McMahon, {Francis J.} and Schulze, {Thomas G.} and Marcella Rietschel and N{\"o}then, {Markus M.} and Sven Cichon",
note = "Funding Information: We are grateful to all patients and control subjects for their participation. We thank the International Consortium on Lithium Genetics (ConLiGen) for providing access to the relevant data. The study was supported by the German Federal Ministry of Education and Research (BMBF) through the Integrated Network IntegraMent (Integrated Understanding of Causes and Mechanisms in Mental Disorders), under the auspices of the e:Med Programme (grant 01ZX1314A/01ZX1614A to MN and SC, grant 01ZX1314G/01ZX1614G to MR). The study was also supported by the German Research Foundation (DFG; grant FOR2107; RI908/11-1 to MR; NO246/10-1 to MN), and the Swiss National Science Foundation (SNSF, grant 310030_156791 to SC). MMN is a member of the DFG-funded Excellence-Cluster ImmunoSensation. AF received support from the BONFOR program of the Medical Faculty of the University of Bonn. The collection of the Geneva sample was supported by the Swiss National Foundation (grants Synapsy 51NF40-158776 and 32003B-125469). The Australian sample contribution was supported by the Australian National Health and Medical Research Council (grants 1037196, 1063960) and the Janette Mary O'Neil Research Fellowship to JF. Publisher Copyright: {\textcopyright} 2018 Reinbold and et al.",
year = "2018",
month = may,
day = "31",
doi = "10.3389/fpsyt.2018.00207",
language = "English",
volume = "9",
journal = "Frontiers in Psychiatry",
issn = "1664-0640",
publisher = "Frontiers Research Foundation",
number = "MAY",
}
TY - JOUR
T1 - Analysis of the influence of microRNAs in lithium response in bipolar disorder
AU - Reinbold, Céline S.
AU - Forstner, Andreas J.
AU - Hecker, Julian
AU - Fullerton, Janice M.
AU - Hoffmann, Per
AU - Hou, Liping
AU - Heilbronner, Urs
AU - Degenhardt, Franziska
AU - Adli, Mazda
AU - Akiyama, Kazufumi
AU - Akula, Nirmala
AU - Ardau, Raffaella
AU - Arias, Bárbara
AU - Backlund, Lena
AU - Benabarre, Antonio
AU - Bengesser, Susanne
AU - Bhattacharjee, Abesh K.
AU - Biernacka, Joanna M.
AU - Birner, Armin
AU - Marie-Claire, Cynthia
AU - Cervantes, Pablo
AU - Chen, Guo Bo
AU - Chen, Hsi Chung
AU - Chillotti, Caterina
AU - Clark, Scott R.
AU - Colom, Francesc
AU - Cousins, David A.
AU - Cruceanu, Cristiana
AU - Czerski, Piotr M.
AU - Dayer, Alexandre
AU - Étain, Bruno
AU - Falkai, Peter
AU - Frisén, Louise
AU - Gard, Sébastien
AU - Garnham, Julie S.
AU - Goes, Fernando S.
AU - Grof, Paul
AU - Gruber, Oliver
AU - Hashimoto, Ryota
AU - Hauser, Joanna
AU - Herms, Stefan
AU - Jamain, Stéphane
AU - Jiménez, Esther
AU - Kahn, Jean Pierre
AU - Kassem, Layla
AU - Kittel-Schneider, Sarah
AU - Kliwicki, Sebastian
AU - König, Barbara
AU - Kusumi, Ichiro
AU - Lackner, Nina
AU - Laje, Gonzalo
AU - Landén, Mikael
AU - Lavebratt, Catharina
AU - Leboyer, Marion
AU - Leckband, Susan G.
AU - Jaramillo, Carlos A.López
AU - MacQueen, Glenda
AU - Manchia, Mirko
AU - Martinsson, Lina
AU - Mattheisen, Manuel
AU - McCarthy, Michael J.
AU - McElroy, Susan L.
AU - Mitjans, Marina
AU - Mondimore, Francis M.
AU - Monteleone, Palmiero
AU - Nievergelt, Caroline M.
AU - Ösby, Urban
AU - Ozaki, Norio
AU - Perlis, Roy H.
AU - Pfennig, Andrea
AU - Reich-Erkelenz, Daniela
AU - Rouleau, Guy A.
AU - Schofield, Peter R.
AU - Schubert, K. Oliver
AU - Schweizer, Barbara W.
AU - Seemüller, Florian
AU - Severino, Giovanni
AU - Shekhtman, Tatyana
AU - Shilling, Paul D.
AU - Shimoda, Kazutaka
AU - Simhandl, Christian
AU - Slaney, Claire M.
AU - Smoller, Jordan W.
AU - Squassina, Alessio
AU - Stamm, Thomas J.
AU - Stopkova, Pavla
AU - Tighe, Sarah K.
AU - Tortorella, Alfonso
AU - Turecki, Gustavo
AU - Volkert, Julia
AU - Witt, Stephanie H.
AU - Wright, Adam J.
AU - Trevor Young, L.
AU - Zandi, Peter P.
AU - Potash, James B.
AU - DePaulo, J. Raymond
AU - Bauer, Michael
AU - Reininghaus, Eva
AU - Novák, Tomáš
AU - Aubry, Jean Michel
AU - Maj, Mario
AU - Baune, Bernhard T.
AU - Mitchell, Philip B.
AU - Vieta, Eduard
AU - Frye, Mark A.
AU - Rybakowski, Janusz K.
AU - Kuo, Po Hsiu
AU - Kato, Tadafumi
AU - Grigoroiu-Serbanescu, Maria
AU - Reif, Andreas
AU - Zompo, Maria Del
AU - Bellivier, Frank
AU - Schalling, Martin
AU - Wray, Naomi R.
AU - Kelsoe, John R.
AU - Alda, Martin
AU - McMahon, Francis J.
AU - Schulze, Thomas G.
AU - Rietschel, Marcella
AU - Nöthen, Markus M.
AU - Cichon, Sven
N1 - Funding Information:
We are grateful to all patients and control subjects for their participation. We thank the International Consortium on Lithium Genetics (ConLiGen) for providing access to the relevant data. The study was supported by the German Federal Ministry of Education and Research (BMBF) through the Integrated Network IntegraMent (Integrated Understanding of Causes and Mechanisms in Mental Disorders), under the auspices of the e:Med Programme (grant 01ZX1314A/01ZX1614A to MN and SC, grant 01ZX1314G/01ZX1614G to MR). The study was also supported by the German Research Foundation (DFG; grant FOR2107; RI908/11-1 to MR; NO246/10-1 to MN), and the Swiss National Science Foundation (SNSF, grant 310030_156791 to SC). MMN is a member of the DFG-funded Excellence-Cluster ImmunoSensation. AF received support from the BONFOR program of the Medical Faculty of the University of Bonn. The collection of the Geneva sample was supported by the Swiss National Foundation (grants Synapsy 51NF40-158776 and 32003B-125469). The Australian sample contribution was supported by the Australian National Health and Medical Research Council (grants 1037196, 1063960) and the Janette Mary O'Neil Research Fellowship to JF.
Publisher Copyright:
© 2018 Reinbold and et al.
PY - 2018/5/31
Y1 - 2018/5/31
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85047859367&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85047859367&partnerID=8YFLogxK
U2 - 10.3389/fpsyt.2018.00207
DO - 10.3389/fpsyt.2018.00207
M3 - Article
AN - SCOPUS:85047859367
SN - 1664-0640
VL - 9
JO - Frontiers in Psychiatry
JF - Frontiers in Psychiatry
IS - MAY
M1 - 207
ER -
