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Focal adhesion is associated with lithium response in bipolar disorder: evidence from a network-based multi-omics analysis.
Niemsiri, Vipavee; Rosenthal, Sara Brin; Nievergelt, Caroline M; Maihofer, Adam X; Marchetto, Maria C; Santos, Renata; Shekhtman, Tatyana; Alliey-Rodriguez, Ney; Anand, Amit; Balaraman, Yokesh; Berrettini, Wade H; Bertram, Holli; Burdick, Katherine E; Calabrese, Joseph R; Calkin, Cynthia V; Conroy, Carla; Coryell, William H; DeModena, Anna; Eyler, Lisa T; Feeder, Scott; Fisher, Carrie; Frazier, Nicole; Frye, Mark A; Gao, Keming; Garnham, Julie; Gershon, Elliot S; Goes, Fernando S; Goto, Toyomi; Harrington, Gloria J; Jakobsen, Petter; Kamali, Masoud; Kelly, Marisa; Leckband, Susan G; Lohoff, Falk W; McCarthy, Michael J; McInnis, Melvin G; Craig, David; Millett, Caitlin E; Mondimore, Francis; Morken, Gunnar; Nurnberger, John I; Donovan, Claire O'; Øedegaard, Ketil J; Ryan, Kelly; Schinagle, Martha; Shilling, Paul D; Slaney, Claire; Stapp, Emma K; Stautland, Andrea; Tarwater, Bruce.
Affiliation
  • Niemsiri V; Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
  • Rosenthal SB; Center for Computational Biology and Bioinformatics, University of California, San Diego, La Jolla, CA, USA.
  • Nievergelt CM; Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
  • Maihofer AX; Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
  • Marchetto MC; Department of Anthropology, University of California, San Diego, La Jolla, CA, USA.
  • Santos R; Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA, USA.
  • Shekhtman T; Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA, USA.
  • Alliey-Rodriguez N; University of Paris, Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1261266, Laboratory of Dynamics of Neuronal Structure in Health and Disease, Paris, France.
  • Anand A; Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
  • Balaraman Y; Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
  • Berrettini WH; Department of Psychiatry and Behavioral Neuroscience, Northwestern University, Chicago, IL, USA.
  • Bertram H; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Burdick KE; Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Calabrese JR; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Calkin CV; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
  • Conroy C; Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
  • Coryell WH; Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • DeModena A; Mood Disorders Program, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
  • Eyler LT; Mood Disorders Program, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
  • Feeder S; Department of Psychiatry and Medical Neuroscience, Dalhousie University, Halifax, NS, Canada.
  • Fisher C; Mood Disorders Program, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
  • Frazier N; Mood Disorders Program, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
  • Frye MA; Department of Psychiatry, University of Iowa, Iowa City, IA, USA.
  • Gao K; Psychiatry Service, VA San Diego Healthcare System, San Diego, CA, USA.
  • Garnham J; Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
  • Gershon ES; Department of Psychiatry, The Mayo Clinic, Rochester, MN, USA.
  • Goes FS; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Goto T; Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
  • Harrington GJ; Department of Psychiatry, The Mayo Clinic, Rochester, MN, USA.
  • Jakobsen P; Mood Disorders Program, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
  • Kamali M; Mood Disorders Program, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
  • Kelly M; Department of Psychiatry, Dalhousie University, Halifax, NS, Canada.
  • Leckband SG; Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
  • Lohoff FW; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
  • McCarthy MJ; Mood Disorders Program, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
  • McInnis MG; Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
  • Craig D; Norment, Division of Psychiatry, Haukeland University Hospital and Department of Clinical medicine, University of Bergen, Bergen, Norway.
  • Millett CE; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Mondimore F; Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
  • Morken G; Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
  • Nurnberger JI; Psychiatry Service, VA San Diego Healthcare System, San Diego, CA, USA.
  • Donovan CO; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
  • Øedegaard KJ; Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
  • Ryan K; Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
  • Schinagle M; Department of Translational Genomics, University of Southern California, Los Angeles, CA, USA.
  • Shilling PD; Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Slaney C; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
  • Stapp EK; Division of Mental Health Care, St Olavs University Hospital, and Department of Mental Health, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
  • Stautland A; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Tarwater B; Medical and Molecular Genetics, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
Mol Psychiatry ; 2023 Mar 29.
Article de En | MEDLINE | ID: mdl-36991131
ABSTRACT
Lithium (Li) is one of the most effective drugs for treating bipolar disorder (BD), however, there is presently no way to predict response to guide treatment. The aim of this study is to identify functional genes and pathways that distinguish BD Li responders (LR) from BD Li non-responders (NR). An initial Pharmacogenomics of Bipolar Disorder study (PGBD) GWAS of lithium response did not provide any significant results. As a result, we then employed network-based integrative analysis of transcriptomic and genomic data. In transcriptomic study of iPSC-derived neurons, 41 significantly differentially expressed (DE) genes were identified in LR vs NR regardless of lithium exposure. In the PGBD, post-GWAS gene prioritization using the GWA-boosting (GWAB) approach identified 1119 candidate genes. Following DE-derived network propagation, there was a highly significant overlap of genes between the top 500- and top 2000-proximal gene networks and the GWAB gene list (Phypergeometric = 1.28E-09 and 4.10E-18, respectively). Functional enrichment analyses of the top 500 proximal network genes identified focal adhesion and the extracellular matrix (ECM) as the most significant functions. Our findings suggest that the difference between LR and NR was a much greater effect than that of lithium. The direct impact of dysregulation of focal adhesion on axon guidance and neuronal circuits could underpin mechanisms of response to lithium, as well as underlying BD. It also highlights the power of integrative multi-omics analysis of transcriptomic and genomic profiling to gain molecular insights into lithium response in BD.
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Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Type d'étude: Guideline / Prognostic_studies / Risk_factors_studies Langue: En Journal: Mol Psychiatry Sujet du journal: BIOLOGIA MOLECULAR / PSIQUIATRIA Année: 2023 Type de document: Article Pays d'affiliation: États-Unis d'Amérique
Texte intégral
Ajouter à My VHL
Imprimer
XML
PubMed Links
Recherche sur Google

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Type d'étude: Guideline / Prognostic_studies / Risk_factors_studies Langue: En Journal: Mol Psychiatry Sujet du journal: BIOLOGIA MOLECULAR / PSIQUIATRIA Année: 2023 Type de document: Article Pays d'affiliation: États-Unis d'Amérique