Lithium response in bipolar disorder is associated with focal adhesion and PI3K-Akt networks: a multi-omics replication study

Author:

Ou Anna H.ORCID,Rosenthal Sara B.,Adli Mazda,Akiyama Kazufumi,Akula Nirmala,Alda MartinORCID,Amare Azmeraw T.ORCID,Ardau Raffaella,Arias BárbaraORCID,Aubry Jean-Michel,Backlund Lena,Bauer MichaelORCID,Baune Bernhard T.ORCID,Bellivier Frank,Benabarre Antonio,Bengesser Susanne,Bhattacharjee Abesh Kumar,Biernacka Joanna M.ORCID,Cervantes Pablo,Chen Guo-Bo,Chen Hsi-ChungORCID,Chillotti Caterina,Cichon Sven,Clark Scott R.ORCID,Colom Francesc,Cousins David A.,Cruceanu CristianaORCID,Czerski Piotr M.ORCID,Dantas Clarissa R.,Dayer Alexandre,Del Zompo MariaORCID,Degenhardt Franziska,DePaulo J. RaymondORCID,Étain BrunoORCID,Falkai Peter,Fellendorf Frederike Tabea,Ferensztajn-Rochowiak Ewa,Forstner Andreas J.ORCID,Frisén Louise,Frye Mark A.ORCID,Fullerton Janice M.ORCID,Gard Sébastien,Garnham Julie S.ORCID,Goes Fernando S.,Grigoroiu-Serbanescu MariaORCID,Grof Paul,Gruber Oliver,Hashimoto RyotaORCID,Hauser JoannaORCID,Heilbronner UrsORCID,Herms Stefan,Hoffmann Per,Hofmann Andrea,Hou LipingORCID,Jamain StephaneORCID,Jiménez Esther,Kahn Jean-Pierre,Kassem Layla,Kato TadafumiORCID,Kittel-Schneider Sarah,König Barbara,Kuo Po-HsiuORCID,Kusumi IchiroORCID,Lackner Nina,Laje Gonzalo,Landén MikaelORCID,Lavebratt CatharinaORCID,Leboyer MarionORCID,Leckband Susan G.,Jaramillo Carlos A. López,MacQueen Glenda,Maj Mario,Manchia MirkoORCID,Marie-Claire CynthiaORCID,Martinsson Lina,Mattheisen Manuel,McCarthy Michael J.,McElroy Susan L.,McMahon Francis J.ORCID,Mitchell Philip B.ORCID,Mitjans MarinaORCID,Mondimore Francis M.,Monteleone Palmiero,Nievergelt Caroline M.ORCID,Nöthen Markus M.ORCID,Novák TomasORCID,Ösby Urban,Ozaki NorioORCID,Papiol SergiORCID,Perlis Roy H.,Pisanu Claudia,Potash James B.,Pfennig Andrea,Reich-Erkelenz Daniela,Reif AndreasORCID,Reininghaus Eva Z.ORCID,Rietschel MarcellaORCID,Rouleau Guy A.ORCID,Rybakowski Janusz K.ORCID,Schalling MartinORCID,Schofield Peter R.ORCID,Schubert K. OliverORCID,Schulze Thomas G.ORCID,Schweizer Barbara W.,Seemüller Florian,Severino GiovanniORCID,Shekhtman Tatyana,Shilling Paul D.ORCID,Shimoda KazutakaORCID,Simhandl Christian,Slaney Claire M.,Squassina AlessioORCID,Stamm Thomas,Stopkova Pavla,Tighe Sarah K.,Tortorella Alfonso,Turecki GustavoORCID,Vieta EduardORCID,Volkert Julia,Witt StephanieORCID,Wray Naomi R.ORCID,Wright Adam,Young L. Trevor,Zandi Peter P.,Kelsoe John R.

Abstract

AbstractLithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.

Publisher

Springer Science and Business Media LLC

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3