Evidence map›Paper›PMID 26806518›Full record

Trial reportLancet (London, England)2016

Genetic variants associated with response to lithium treatment in bipolar disorder: a genome-wide association study.

Liping Hou, Urs Heilbronner, Franziska Degenhardt, Mazda Adli, Kazufumi Akiyama, Nirmala Akula, Raffaella Ardau, Bárbara Arias, Lena Backlund, Claudio E M Banzato and 113 more

Open access · greenAbstract readClinical TrialMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Lancet (London, England), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 164 papers, 9 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
164citing papers in PubMed, 9 pooled it
34.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

164 citing papers in PubMed, 9 syntheses or guidelines pooled it, 396 citations in OpenAlex.

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  10. Prediction of lithium treatment response in bipolar depression using 5-HTT and 5-HTEuropean journal of nuclear medicine and molecular imaging · 2020
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104 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

123 authors at 20 institutions in 19 countries.

Liping HouIntramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health & Human Services, Bethesda, MD, USA.
Urs HeilbronnerInstitute of Psychiatric Phenomics and Genomics, Ludwig-Maximilians-University Munich, Munich, Germany; Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August University Göttingen, Göttingen, Germany.
Franziska DegenhardtInstitute of Human Genetics, University of Bonn and Department of Genomics, Life & Brain Center, Bonn, Germany.
Mazda AdliDepartment of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany; Fliedner Klinik Berlin, Center for Psychiatry, Psychotherapy and Psychosomatic Medicine, Berlin, Germany.
Kazufumi AkiyamaDepartment of Biological Psychiatry and Neuroscience, Dokkyo Medical University School of Medicine, Mibu, Japan.
Nirmala AkulaIntramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health & Human Services, Bethesda, MD, USA.
Raffaella ArdauUnit of Clinical Pharmacology, Hospital University Agency of Cagliari, Cagliari, Italy.
Bárbara AriasDepartment of Biologia Animal, Unitat d'Antropologia (Dp Biología Animal), Facultat de Biologia and Institut de Biomedicina (IBUB), Universitat de Barcelona, CIBERSAM, Barcelona, Catalonia, Spain.
Lena BacklundDepartment of Molecular Medicine and Surgery, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
Claudio E M BanzatoDepartment of Psychiatry, University of Campinas (Unicamp), Campinas, Brazil.
Antoni BenabarreBipolar Disorder Program, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain.
Susanne BengesserNeurobiological Background and Anthropometrics in Bipolar Affective Disorder, Department of Psychiatry, Medical University of Graz, Graz, Austria.
Abesh Kumar BhattacharjeeDepartment of Psychiatry, University of California San Diego, San Diego, CA, USA.
Joanna M BiernackaDepartment of Health Sciences Research, Mayo Clinic, Rochester, MN, USA; Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.
Armin BirnerNeurobiological Background and Anthropometrics in Bipolar Affective Disorder, Department of Psychiatry, Medical University of Graz, Graz, Austria.
Clara Brichant-PetitjeanINSERM UMR-S 1144-Université Paris Diderot Pôle de Psychiatrie, AP-HP, Groupe Hospitalier Lariboisière-F Widal, Paris, France.
Elise T BuiIntramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health & Human Services, Bethesda, MD, USA.
Pablo CervantesThe Neuromodulation Unit, McGill University Health Centre, Montreal, QC, Canada.
Guo-Bo ChenThe University of Queensland, Queensland Brain Institute, Brisbane, Queensland, QLD, Australia.
Hsi-Chung ChenDepartment of Psychiatry & Center of Sleep Disorders, National Taiwan University Hospital, Taipei, Taiwan.
Caterina ChillottiUnit of Clinical Pharmacology, Hospital University Agency of Cagliari, Cagliari, Italy.
Sven CichonInstitute of Human Genetics, University of Bonn and Department of Genomics, Life & Brain Center, Bonn, Germany; Human Genomics Research Group, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
Scott R ClarkDiscipline of Psychiatry, University of Adelaide, Adelaide, SA, Australia.
Francesc ColomBipolar Disorder Program, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain.
David A CousinsCampus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UK.
Cristiana CruceanuDouglas Mental Health University Institute, McGill University, Montreal, QC, Canada.
Piotr M CzerskiPsychiatric Genetic Unit, Poznan University of Medical Sciences, Poznan, Poland.
Clarissa R DantasDepartment of Psychiatry, University of Campinas (Unicamp), Campinas, Brazil.
Alexandre DayerDepartment of Mental Health and Psychiatry, Mood Disorders Unit-Geneva University Hospitals, Geneva, Switzerland.
Bruno ÉtainInserm U955, Psychiatrie Translationnelle, Créteil, France.
Peter FalkaiDepartment of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Munich, Germany.
Andreas J ForstnerInstitute of Human Genetics, University of Bonn and Department of Genomics, Life & Brain Center, Bonn, Germany.
Louise FrisénDepartment of Molecular Medicine and Surgery, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden; Child and Adolescent Psychiatry Research Center, Stockholm, Sweden.
Janice M FullertonMental Illness Research Theme, Neuroscience Research Australia, Sydney, NSW, Australia; School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
Sébastien GardPôle de Psychiatrie Générale Universitaire, Centre Hospitalier Charles Perrens, Bordeaux, France.
Julie S GarnhamDepartment of Psychiatry, Dalhousie University, Halifax, Nova Scotia, NS, Canada.
Fernando S GoesDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
Paul GrofMood Disorders Center of Ottawa, Ottawa, ON, Canada.
Oliver GruberDepartment of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August University Göttingen, Göttingen, Germany.
Ryota HashimotoMolecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Osaka, Japan.
Joanna HauserPsychiatric Genetic Unit, Poznan University of Medical Sciences, Poznan, Poland.
Stefan HermsInstitute of Human Genetics, University of Bonn and Department of Genomics, Life & Brain Center, Bonn, Germany; Human Genomics Research Group, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
Per HoffmannInstitute of Human Genetics, University of Bonn and Department of Genomics, Life & Brain Center, Bonn, Germany; Human Genomics Research Group, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
Andrea HofmannInstitute of Human Genetics, University of Bonn and Department of Genomics, Life & Brain Center, Bonn, Germany.
Stephane JamainInserm U955, Psychiatrie Translationnelle, Créteil, France.
Esther JiménezBipolar Disorder Program, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain.
Jean-Pierre KahnService de Psychiatrie et Psychologie Clinique, Centre Psychothérapique de Nancy-Laxou-Université de Lorraine, Nancy, France.
Layla KassemIntramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health & Human Services, Bethesda, MD, USA.
Sarah Kittel-SchneiderDepartment of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany.
Sebastian KliwickiDepartment of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
Barbara KönigDepartment of Psychiatry and Psychotherapeutic Medicine, Landesklinikum Neunkirchen, Neunkirchen, Austria.
Ichiro KusumiDepartment of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Nina LacknerNeurobiological Background and Anthropometrics in Bipolar Affective Disorder, Department of Psychiatry, Medical University of Graz, Graz, Austria.
Gonzalo LajeIntramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health & Human Services, Bethesda, MD, USA.
Mikael LandénInstitute of Neuroscience and Physiology, The Sahlgrenska Academy at the Gothenburg University, Gothenburg, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Catharina LavebrattDepartment of Molecular Medicine and Surgery, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
Marion LeboyerAssistance Publique-Hôpitaux de Paris, Hôpital Albert Chenevier-Henri Mondor, Pôle de Psychiatrie, Créteil, France.
Susan G LeckbandDepartment of Molecular Medicine and Surgery, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden; Department of Pharmacy, VA San Diego Healthcare System, San Diego, CA, USA.
Carlos A López JaramilloDepartment of Psychiatry, University of Antioquia, Medellín, Medellín, Colombia.
Glenda MacQueenDepartment of Psychiatry, University of Calgary, Calgary, AB, Canada.
Mirko ManchiaDepartment of Biomedical Sciences, University of Cagliari, Cagliari, Italy; Department of Pharmacology, Dalhousie University, Halifax, NS, Canada.
Lina MartinssonDepartment of Clinical Neurosciences, Karolinska Institutet, Stockholm, Sweden.
Manuel MattheisenDepartment of Biomedicine, Aarhus University, Aarhus, Denmark.
Michael J McCarthyDepartment of Psychiatry, VA San Diego Healthcare System, San Diego, CA, USA.
Susan L McElroyDepartment of Psychiatry, Lindner Center of Hope, University of Cincinnati, Mason, OH, USA.
Marina MitjansDepartment of Biologia Animal, Unitat d'Antropologia (Dp Biología Animal), Facultat de Biologia and Institut de Biomedicina (IBUB), Universitat de Barcelona, CIBERSAM, Barcelona, Catalonia, Spain.
Francis M MondimoreDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
Palmiero MonteleoneNeurosciences Section, Department of Medicine and Surgery, University of Salerno, Salerno, Italy; Department of Psychiatry, University of Naples SUN, Naples, Italy.
Caroline M NievergeltDepartment of Psychiatry, University of California San Diego, San Diego, CA, USA.
Markus M NöthenInstitute of Human Genetics, University of Bonn and Department of Genomics, Life & Brain Center, Bonn, Germany.
Urban ÖsbyDepartment of Neurobiology, Care sciences, and Society, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
Norio OzakiDepartment of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Roy H PerlisDepartment of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Andrea PfennigDepartment of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany.
Daniela Reich-ErkelenzInstitute of Psychiatric Phenomics and Genomics, Ludwig-Maximilians-University Munich, Munich, Germany.
Guy A RouleauMontreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada.
Peter R SchofieldMental Illness Research Theme, Neuroscience Research Australia, Sydney, NSW, Australia; School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
K Oliver SchubertDiscipline of Psychiatry, University of Adelaide, Adelaide, SA, Australia.
Barbara W SchweizerDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
Florian SeemüllerDepartment of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Munich, Germany.
Giovanni SeverinoDepartment of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
Tatyana ShekhtmanVeterans Administration, San Diego Healthcare System, San Diego, CA, USA; Department of Psychiatry, University of California San Diego, San Diego, CA, USA.
Paul D ShillingDepartment of Psychiatry, University of California San Diego, San Diego, CA, USA.
Kazutaka ShimodaDepartment of Psychiatry, Dokkyo Medical University School of Medicine, Mibu, Japan.
Christian SimhandlBipolar Center Wiener Neustadt, Wiener Neustadt, Austria.
Claire M SlaneyDepartment of Psychiatry, Dalhousie University, Halifax, Nova Scotia, NS, Canada.
Jordan W SmollerDepartment of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Alessio SquassinaDepartment of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
Thomas StammDepartment of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany.
Pavla StopkovaNational Institute of Mental Health, Klecany, Czech Republic.
Sarah K TigheDepartment of Psychiatry, University of Iowa, Iowa City, IA, USA; University of Iowa Carver College of Medicine and University of Iowa College of Public Health, VA Quality Scholars Program, Iowa City VA Hospital, Iowa City, IA, USA.
Alfonso TortorellaDepartment of Psychiatry, University of Naples SUN, Naples, Italy.
Gustavo TureckiDouglas Mental Health University Institute, McGill University, Montreal, QC, Canada.
Julia VolkertDepartment of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany.
Stephanie WittDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Adam WrightSchool of Psychiatry, University of New South Wales, and Black Dog Institute, Sydney, NSW, Australia.
L Trevor YoungDepartment of Psychiatry, University of Toronto, Toronto, ON, Canada.
Peter P ZandiDepartment of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
James B PotashDepartment of Psychiatry, University of Iowa, Iowa City, IA, USA.
J Raymond DePauloDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
Michael BauerDepartment of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany.
Eva Z ReininghausNeurobiological Background and Anthropometrics in Bipolar Affective Disorder, Department of Psychiatry, Medical University of Graz, Graz, Austria.
Tomas NovákNational Institute of Mental Health, Klecany, Czech Republic.
Jean-Michel AubryDepartment of Mental Health and Psychiatry, Mood Disorders Unit-Geneva University Hospitals, Geneva, Switzerland.
Mario MajDepartment of Psychiatry, University of Naples SUN, Naples, Italy.
Bernhard T BauneDiscipline of Psychiatry, University of Adelaide, Adelaide, SA, Australia.
Philip B MitchellSchool of Psychiatry, University of New South Wales, and Black Dog Institute, Sydney, NSW, Australia.
Eduard VietaBipolar Disorder Program, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain.
Mark A FryeDepartment of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.
Janusz K RybakowskiDepartment of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
Po-Hsiu KuoInstitute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan.
Tadafumi KatoLaboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, Saitama, Japan.
Maria Grigoroiu-SerbanescuBiometric Psychiatric Genetics Research Unit, Alexandru Obregia Psychiatric Hospital, Bucharest, Romania.
Andreas ReifDepartment of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany.
Maria Del ZompoUnit of Clinical Pharmacology, Hospital University Agency of Cagliari, Cagliari, Italy; Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
Frank BellivierINSERM UMR-S 1144-Université Paris Diderot Pôle de Psychiatrie, AP-HP, Groupe Hospitalier Lariboisière-F Widal, Paris, France.
Martin SchallingDepartment of Molecular Medicine and Surgery, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
Naomi R WrayThe University of Queensland, Queensland Brain Institute, Brisbane, Queensland, QLD, Australia.
John R KelsoeVeterans Administration, San Diego Healthcare System, San Diego, CA, USA; Department of Psychiatry, University of California San Diego, San Diego, CA, USA.
Martin AldaDepartment of Psychiatry, Dalhousie University, Halifax, Nova Scotia, NS, Canada; National Institute of Mental Health, Klecany, Czech Republic.
Marcella RietschelDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Francis J McMahonIntramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health & Human Services, Bethesda, MD, USA. Electronic address: mcmahonf@mail.nih.gov.
Thomas G SchulzeIntramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health & Human Services, Bethesda, MD, USA; Institute of Psychiatric Phenomics and Genomics, Ludwig-Maximilians-University Munich, Munich, Germany; Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August University Göttingen, Göttingen, Germany; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany. Electronic address: thomas.schulze@med.uni-muenchen.de.
Karolinska Institutet · SEUniversity of Cagliari · ITJohns Hopkins University · USMedical University of Graz · ATPoznan University of Medical Sciences · PLUniversitat de Barcelona · ESUniversity of Bonn · DEUNSW Sydney · AUDalhousie University · CAInserm · FRLudwig-Maximilians-Universität München · DEUnited States Department of Health and Human Services · USUniversity of Adelaide · AUUniversity of California, San Diego · USVA San Diego Healthcare System · USAssistance Publique – Hôpitaux de Paris · FRCentro de Investigación Biomédica en Red de Salud Mental · ESCharité - Universitätsmedizin Berlin · DEDokkyo Medical University · JPHarvard University · US

Funding

Mapping genes that contribute to bipolar disorderZIAMH002810 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI MCMAHON, FRANCIS J · 2009 to 2025
$31.2M
Identification of Genes Involved in Major Mood DisordersZIAMH002843 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI MCMAHON, FRANCIS J · 2009 to 2025
$24.5M
The Collaborative Genetic Study of Nicotine DependenceP01CA089392 · NCI · WASHINGTON UNIVERSITY · PI BIERUT, LAURA J. · 2001 to 2012
$17.3M
COLLABORATIVE GENOMIC STUDY OF BIPOLAR DISORDERR01MH059534 · NIMH · WASHINGTON UNIVERSITY · PI RICE, JOHN P. · 1998 to 2007
$3.1M
COLLABORATIVE GENOMIC STUDY OF BIPOLAR DISORDERR01MH059545 · NIMH · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI NURNBERGER, JOHN I · 1998 to 2007
$2.6M
COLLABORATIVE GENOMIC STUDY OF BIPOLAR DISORDERR01MH059533 · NIMH · JOHNS HOPKINS UNIVERSITY · PI MACKINNON, DEAN FREDERICK · 1998 to 2007
$2.4M
COLLABORATIVE GENOMIC STUDY OF BIPOLAR DISORDERR01MH060068 · NIMH · UNIVERSITY OF CALIFORNIA IRVINE · PI BYERLEY, WILLIAM · 1998 to 2007
$2.1M
COLLABORATIVE GENOMIC STUDY OF BIPOLAR DISORDERR01MH059553 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI BERRETTINI, WADE H · 1998 to 2007
$2.1M
Mapping genes that contribute to bipolar disorderZ01MH002810 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI MCMAHON, FRANCIS J · 2003 to 2008
$2.0M
Collaborative Genomic Study of Bipolar DisorderR01MH059548 · NIMH · UNIVERSITY OF IOWA · PI CORYELL, WILLIAM HENRY · 1998 to 2007
$1.9M
COLLABORATIVE STUDY OF BIPOLAR DISORDERR01MH059535 · NIMH · UNIVERSITY OF CHICAGO · PI GERSHON, ELLIOT S · 1998 to 2007
$1.9M
COLLABORATIVE GENOMIC STUDY OF BIPOLAR DISORDERR01MH059567 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KELSOE, JOHN R. · 1998 to 2007
$1.8M
CIHR 64410Intramural NIH HHS Z01 MH002810Intramural NIH HHS Z99 MH999999Medical Research Council MR/L006642/1NCI NIH HHS P01 CA089392NCI NIH HHS P50CA89392NIDA NIH HHS 5K02DA021237NIDA NIH HHS K02 DA021237NIDA NIH HHS K02 DA21237NIMH NIH HHS 1Z01MH002810-01NIMH NIH HHS R01 MH059533NIMH NIH HHS R01 MH059534NIMH NIH HHS R01 MH059535NIMH NIH HHS R01 MH059545NIMH NIH HHS R01 MH059548NIMH NIH HHS R01 MH059553NIMH NIH HHS R01 MH059556NIMH NIH HHS R01 MH059567NIMH NIH HHS R01 MH060068NIMH NIH HHS R01 MH59533NIMH NIH HHS R01 MH59535NIMH NIH HHS R01 MH59545NIMH NIH HHS R01 MH59553NIMH NIH HHS R01 MH59567NIMH NIH HHS R01 MH60068NIMH NIH HHS ZIA-MH00284311
6 · The paper itself

Abstract

backgroundLithium is a first-line treatment in bipolar disorder, but individual response is variable. Previous studies have suggested that lithium response is a heritable trait. However, no genetic markers of treatment response have been reproducibly identified.

methodsHere, we report the results of a genome-wide association study of lithium response in 2563 patients collected by 22 participating sites from the International Consortium on Lithium Genetics (ConLiGen). Data from common single nucleotide polymorphisms (SNPs) were tested for association with categorical and continuous ratings of lithium response. Lithium response was measured using a well established scale (Alda scale). Genotyped SNPs were used to generate data at more than 6 million sites, using standard genomic imputation methods. Traits were regressed against genotype dosage. Results were combined across two batches by meta-analysis.

findingsA single locus of four linked SNPs on chromosome 21 met genome-wide significance criteria for association with lithium response (rs79663003, p=1·37 × 10(-8); rs78015114, p=1·31 × 10(-8); rs74795342, p=3·31 × 10(-9); and rs75222709, p=3·50 × 10(-9)). In an independent, prospective study of 73 patients treated with lithium monotherapy for a period of up to 2 years, carriers of the response-associated alleles had a significantly lower rate of relapse than carriers of the alternate alleles (p=0·03268, hazard ratio 3·8, 95% CI 1·1-13·0).

interpretationThe response-associated region contains two genes for long, non-coding RNAs (lncRNAs), AL157359.3 and AL157359.4. LncRNAs are increasingly appreciated as important regulators of gene expression, particularly in the CNS. Confirmed biomarkers of lithium response would constitute an important step forward in the clinical management of bipolar disorder. Further studies are needed to establish the biological context and potential clinical utility of these findings.

fundingDeutsche Forschungsgemeinschaft, National Institute of Mental Health Intramural Research Program.

Indexed as

Bipolar DisorderFemaleGenetic VariationGenome-Wide Association StudyGenotypeGlial Cell Line-Derived Neurotrophic Factor ReceptorsHumansLithium CompoundsMaleMiddle AgedPhenotypePolymorphism, Single NucleotideProspective StudiesTreatment OutcomeGFRA2 protein, humanGlial Cell Line-Derived Neurotrophic Factor ReceptorsLithium Compounds

Identifiers

PMID26806518
PMCPMC4814312
OpenAlexW2262279506

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.