Exome sequencing in bipolar disorder identifies AKAP11 as a risk gene shared with schizophrenia.

A Kinase Anchor Proteins / genetics Bipolar Disorder / genetics Exome / genetics Genetic Predisposition to Disease Genome-Wide Association Study Humans Schizophrenia / genetics Exome Sequencing

Journal

Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904

Informations de publication

Date de publication:
05 2022
Historique:
received: 03 03 2021
accepted: 15 02 2022
pubmed: 13 4 2022
medline: 20 5 2022
entrez: 12 4 2022
Statut: ppublish

Résumé

We report results from the Bipolar Exome (BipEx) collaboration analysis of whole-exome sequencing of 13,933 patients with bipolar disorder (BD) matched with 14,422 controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in patients with BD among genes under strong evolutionary constraint in both major BD subtypes. We find enrichment of ultra-rare PTVs within genes implicated from a recent schizophrenia exome meta-analysis (SCHEMA; 24,248 cases and 97,322 controls) and among binding targets of CHD8. Genes implicated from genome-wide association studies (GWASs) of BD, however, are not significantly enriched for ultra-rare PTVs. Combining gene-level results with SCHEMA, AKAP11 emerges as a definitive risk gene (odds ratio (OR) = 7.06, P = 2.83 × 10

Identifiants

DOI: 10.1038/s41588-022-01034-x PMID: 35410376 PMC: PMC9117467
pubmed: 35410376
doi: 10.1038/s41588-022-01034-x
pii: 10.1038/s41588-022-01034-x
pmc: PMC9117467
mid: NIHMS1787232
doi:

Substances chimiques

A Kinase Anchor Proteins 0
AKAP11 protein, human 0

Types de publication

Journal Article Meta-Analysis Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

541-547

Subventions

Organisme : Medical Research Council
ID : MR/P005748/1
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : RC2 AG036607
Pays : United States
Organisme : Medical Research Council
ID : MR/L010305/1
Pays : United Kingdom
Organisme : NIMH NIH HHS
ID : R01 MH110437
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH105578
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH085543
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH084676
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA194393
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH090553
Pays : United States
Organisme : Medical Research Council
ID : G1000708
Pays : United Kingdom
Organisme : NIMH NIH HHS
ID : R37 MH107649
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH095034
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH085542
Pays : United States

Informations de copyright

© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.

Références

Ferrari, A. J. et al. The prevalence and burden of bipolar disorder: findings from the Global Burden of Disease Study 2013. Bipolar Disord. 18, 440–450 (2016).
pubmed: 27566286 doi: 10.1111/bdi.12423
Polderman, T. J. C. et al. Meta-analysis of the heritability of human traits based on fifty years of twin studies. Nat. Genet. 47, 702–709 (2015).
pubmed: 25985137 doi: 10.1038/ng.3285
Stahl, E. A. et al. Genome-wide association study identifies 30 loci associated with bipolar disorder. Nat. Genet. 51, 793–803 (2019).
pubmed: 31043756 pmcid: 6956732 doi: 10.1038/s41588-019-0397-8
Brainstorm Consortium. et al. Analysis of shared heritability in common disorders of the brain. Science 360, eaap8757 (2018).
doi: 10.1126/science.aap8757
Mullins, N. et al. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology.Nat. Genet. 53, 817–829 (2021).
pubmed: 34002096 pmcid: 8192451 doi: 10.1038/s41588-021-00857-4
Charney, A. W. et al. Contribution of rare copy number variants to bipolar disorder risk is limited to schizoaffective cases. Biol. Psychiatry 86, 110–119 (2019).
pubmed: 30686506 doi: 10.1016/j.biopsych.2018.12.009
Ganna, A. et al. Quantifying the impact of rare and ultra-rare coding variation across the phenotypic spectrum. Am. J. Hum. Genet. 102, 1204–1211 (2018).
pubmed: 29861106 pmcid: 5992130 doi: 10.1016/j.ajhg.2018.05.002
J., A., Crow, J. F. & Kimura, M. An introduction to population genetics theory. Popul. (Fr. Ed.). 26, 977 (1971).
Kryukov, G. V., Pennacchio, L. A. & Sunyaev, S. R. Most rare missense alleles are deleterious in humans: implications for complex disease and association studies. Am. J. Hum. Genet. 80, 727–739 (2007).
pubmed: 17357078 pmcid: 1852724 doi: 10.1086/513473
Power, R. A. et al. Fecundity of patients with schizophrenia, autism, bipolar disorder, depression, anorexia nervosa, or substance abuse vs their unaffected siblings. JAMA Psychiatry 70, 22–30 (2013).
pubmed: 23147713 doi: 10.1001/jamapsychiatry.2013.268
American Psychiatric Association, Task Force on DSM-IV. DSM-IV Sourcebook (American Psychiatric Publishing, 1998).
Janca, A., Ustün, T. B., Early, T. S. & Sartorius, N. The ICD-10 symptom checklist: a companion to the ICD-10 classification of mental and behavioural disorders. Soc. Psychiatry Psychiatr. Epidemiol. 28, 239–242 (1993).
pubmed: 8284737 doi: 10.1007/BF00788743
Malaspina, D. et al. Schizoaffective disorder in the DSM-5. Schizophr. Res. 150, 21–25 (2013).
pubmed: 23707642 doi: 10.1016/j.schres.2013.04.026
O’Connell, K. S. & Coombes, B. J. Genetic contributions to bipolar disorder: current status and future directions.Psychol. Med. 51, 2156–2167 (2021).
pubmed: 33879273 pmcid: 8477227 doi: 10.1017/S0033291721001252
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (American Psychiatric Publishing, 2013).
Husson, T. et al. Identification of potential genetic risk factors for bipolar disorder by whole-exome sequencing. Transl. Psychiatry 8, 268 (2018).
pubmed: 30518751 pmcid: 6281607 doi: 10.1038/s41398-018-0291-7
Sul, J. H. et al. Contribution of common and rare variants to bipolar disorder susceptibility in extended pedigrees from population isolates. Transl. Psychiatry 10, 74 (2020).
pubmed: 32094344 pmcid: 7039961 doi: 10.1038/s41398-020-0758-1
Jia, X. et al. Investigating rare pathogenic/likely pathogenic exonic variation in bipolar disorder. Mol. Psychiatry 26, 5239–5250 (2021).
pubmed: 33483695 pmcid: 8295400 doi: 10.1038/s41380-020-01006-9
Cruceanu, C. et al. Rare susceptibility variants for bipolar disorder suggest a role for G protein-coupled receptors. Mol. Psychiatry 23, 2050–2056 (2018).
pubmed: 29158579 doi: 10.1038/mp.2017.223
Genovese, G. et al. Increased burden of ultra-rare protein-altering variants among 4,877 individuals with schizophrenia. Nat. Neurosci. 19, 1433–1441 (2016).
pubmed: 27694994 pmcid: 5104192 doi: 10.1038/nn.4402
Singh, T. et al. The contribution of rare variants to risk of schizophrenia in individuals with and without intellectual disability. Nat. Genet. 49, 1167–1173 (2017).
pubmed: 28650482 pmcid: 5533219 doi: 10.1038/ng.3903
McLaren, W. et al. The Ensembl variant effect predictor. Genome Biol. 17, 122 (2016).
pubmed: 27268795 pmcid: 4893825 doi: 10.1186/s13059-016-0974-4
Singh, T. et al. Rare coding variants in ten genes confer substantial risk for schizophrenia. Nature https://doi.org/10.1038/s41586-022-04556-w (2022).
Samocha, K. E., Kosmicki, J. A. & Karczewski, K. J. Regional missense constraint improves variant deleteriousness prediction. Preprint at bioRxiv https://doi.org/10.1101/148353 (2017).
Aguet, F. et al. The GTEx Consortium atlas of genetic regulatory effects across human tissues. Science 369, 1318–1330 (2020).
doi: 10.1126/science.aaz1776
Finucane, H. K. et al. Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types. Nat. Genet. 50, 621–629 (2018).
pubmed: 29632380 pmcid: 5896795 doi: 10.1038/s41588-018-0081-4
Hibar, D. P. et al. Subcortical volumetric abnormalities in bipolar disorder. Mol. Psychiatry 21, 1710–1716 (2016).
pubmed: 26857596 pmcid: 5116479 doi: 10.1038/mp.2015.227
Ganna, A. et al. Ultra-rare disruptive and damaging mutations influence educational attainment in the general population. Nat. Neurosci. 19, 1563–1565 (2016).
pubmed: 27694993 pmcid: 5127781 doi: 10.1038/nn.4404
Cotney, J. et al. The autism-associated chromatin modifier CHD8 regulates other autism risk genes during human neurodevelopment. Nat. Commun. 6, 6404 (2015).
pubmed: 25752243 doi: 10.1038/ncomms7404
Weyn-Vanhentenryck, S. M. et al. HITS-CLIP and integrative modeling define the Rbfox splicing-regulatory network linked to brain development and autism. Cell Rep. 6, 1139–1152 (2014).
pubmed: 24613350 pmcid: 3992522 doi: 10.1016/j.celrep.2014.02.005
Sanders, S. J. et al. Insights into autism spectrum disorder genomic architecture and biology from 71 risk loci. Neuron 87, 1215–1233 (2015).
pubmed: 26402605 pmcid: 4624267 doi: 10.1016/j.neuron.2015.09.016
Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium & Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium. Genomic dissection of bipolar disorder and schizophrenia, including 28 subphenotypes. Cell 173, 1705–1715 (2018).
Trubetskoy, V. et al. Mapping genomic loci implicates genes and synaptic biology in schizophrenia. Nature https://doi.org/10.1038/s41586-022-04434-5 (2022).
Freland, L. & Beaulieu, J.-M. Inhibition of GSK3 by lithium, from single molecules to signaling networks. Front. Mol. Neurosci. 5, 14 (2012).
pubmed: 22363263 pmcid: 3282483 doi: 10.3389/fnmol.2012.00014
Kishore, B. K. & Ecelbarger, C. M. Lithium: a versatile tool for understanding renal physiology. Am. J. Physiol. Ren. Physiol. 304, F1139–F1149 (2013).
doi: 10.1152/ajprenal.00718.2012
Jope, R. S. Lithium and GSK-3: one inhibitor, two inhibitory actions, multiple outcomes. Trends Pharmacol. Sci. 24, 441–443 (2003).
pubmed: 12967765 doi: 10.1016/S0165-6147(03)00206-2
Satterstrom, F. K. et al. Large-scale exome sequencing study implicates both developmental and functional changes in the neurobiology of Autism. Cell 180, 568–584.e23 (2020).
pubmed: 31981491 pmcid: 7250485 doi: 10.1016/j.cell.2019.12.036
Satterstrom, F. K. et al. Autism spectrum disorder and attention deficit hyperactivity disorder have a similar burden of rare protein-truncating variants. Nat. Neurosci. 22, 1961–1965 (2019).
pubmed: 31768057 pmcid: 6884695 doi: 10.1038/s41593-019-0527-8
Epi25 Collaborative. Ultra-rare genetic variation in the epilepsies: a whole-exome sequencing study of 17,606 individuals. Am. J. Hum. Genet. 105, 267–282 (2019).
Firth, H. V. et al. DECIPHER: database of chromosomal imbalance and phenotype in humans using ensembl resources. Am. J. Hum. Genet. 84, 524–533 (2009).
pubmed: 19344873 pmcid: 2667985 doi: 10.1016/j.ajhg.2009.03.010
Tanji, C. et al. A-kinase anchoring protein AKAP220 binds to glycogen synthase kinase-3beta (GSK-3beta) and mediates protein kinase A-dependent inhibition of GSK-3beta. J. Biol. Chem. 277, 36955–36961 (2002).
pubmed: 12147701 doi: 10.1074/jbc.M206210200
Beurel, E., Grieco, S. F. & Jope, R. S. Glycogen synthase kinase-3 (GSK3): regulation, actions, and diseases. Pharmacol. Ther. 148, 114–131 (2015).
pubmed: 25435019 doi: 10.1016/j.pharmthera.2014.11.016
Howrigan, D. P. et al. Exome sequencing in schizophrenia-affected parent-offspring trios reveals risk conferred by protein-coding de novo mutations. Nat. Neurosci. 23, 185–193 (2020).
pubmed: 31932770 pmcid: 7007385 doi: 10.1038/s41593-019-0564-3
Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. 57, 289–300 (1995).
Van der Auwera, G. A. et al. From FastQ data to high confidence variant calls: the Genome Analysis Toolkit best practices pipeline. Curr. Protoc. Bioinforma. 43, 11.10.1–11.10.33 (2013).
doi: 10.1002/0471250953.bi1110s43
DePristo, M. A. et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat. Genet. 43, 491–498 (2011).
pubmed: 21478889 pmcid: 3083463 doi: 10.1038/ng.806
Ng, P. C. & Henikoff, S. SIFT: predicting amino acid changes that affect protein function. Nucleic Acids Res. 31, 3812–3814 (2003).
pubmed: 12824425 pmcid: 168916 doi: 10.1093/nar/gkg509
Adzhubei, I. A. et al. A method and server for predicting damaging missense mutations. Nat. Methods 7, 248–249 (2010).
pubmed: 20354512 pmcid: 2855889 doi: 10.1038/nmeth0410-248
Karczewski, K. J. et al. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature 581, 434–443 (2020).
pubmed: 32461654 pmcid: 7334197 doi: 10.1038/s41586-020-2308-7
Rentzsch, P., Witten, D., Cooper, G. M., Shendure, J. & Kircher, M. CADD: predicting the deleteriousness of variants throughout the human genome. Nucleic Acids Res. 47, D886–D894 (2019).
pubmed: 30371827 doi: 10.1093/nar/gky1016
Chen, C.-Y. et al. Genetic validation of bipolar disorder identified by automated phenotyping using electronic health records. Transl. Psychiatry 8, 86 (2018).
pubmed: 29666432 pmcid: 5904248 doi: 10.1038/s41398-018-0133-7
Murphy, S. et al. Instrumenting the health care enterprise for discovery research in the genomic era. Genome Res. 19, 1675–1681 (2009).
pubmed: 19602638 pmcid: 2752136 doi: 10.1101/gr.094615.109
Wing, J. SCAN (Schedules for Clinical Assessment in Neuropsychiatry) and the PSE (Present State Examination) Tradition. Mental Health Outcome Measures 123–130 (Springer, 1996).
McGuffin, P., Farmer, A. & Harvey, I. A polydiagnostic application of operational criteria in studies of psychotic illness. Development and reliability of the OPCRIT system. Arch. Gen. Psychiatry 48, 764–770 (1991).
pubmed: 1883262 doi: 10.1001/archpsyc.1991.01810320088015

Auteurs

Duncan S Palmer (DS)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. duncan.stuart.palmer@gmail.com.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA. duncan.stuart.palmer@gmail.com.
ORCID: 0000-0002-0824-0047

Daniel P Howrigan (DP)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
ORCID: 0000-0002-7721-4838

Sinéad B Chapman (SB)

Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
ORCID: 0000-0002-9454-2737

Rolf Adolfsson (R)

Department of Clinical Sciences, Psychiatry, Umea University, Umea, Sweden.

Nick Bass (N)

Division of Psychiatry, University College London, London, UK.

Douglas Blackwood (D)

Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
ORCID: 0000-0002-4076-9346

Marco P M Boks (MPM)

Department of Psychiatry, Brain Center UMC Utrecht, Utrecht, the Netherlands.
ORCID: 0000-0001-6163-7484

Chia-Yen Chen (CY)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Biogen, Cambridge, MA, USA.
ORCID: 0000-0001-9548-5597

Claire Churchhouse (C)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Aiden P Corvin (AP)

Trinity College Dublin, Dublin, Ireland.

Nicholas Craddock (N)

MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.

David Curtis (D)

UCL Genetics Institute, University College London, London, UK.
Centre for Psychiatry, Queen Mary University of London, London, UK.
ORCID: 0000-0002-4089-9183

Arianna Di Florio (A)

Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.

Faith Dickerson (F)

Sheppard Pratt, Baltimore, MD, USA.

Nelson B Freimer (NB)

Department of Psychiatry and Biobehavioral Science, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
ORCID: 0000-0003-3586-6587

Fernando S Goes (FS)

Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.
ORCID: 0000-0001-6262-8264

Xiaoming Jia (X)

Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.

Ian Jones (I)

MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
National Centre for Mental Health, Division of Psychiatry and Clinical Neurosciences, Cardiff University, Cardiff, UK.
ORCID: 0000-0001-5821-5889

Lisa Jones (L)

Department of Psychological Medicine, University of Worcester, Worcester, UK.
ORCID: 0000-0002-5122-8334

Lina Jonsson (L)

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Rene S Kahn (RS)

Division of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
ORCID: 0000-0001-5909-8004

Mikael Landén (M)

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
ORCID: 0000-0002-4496-6451

Adam E Locke (AE)

Division of Genomics & Bioinformatics and McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA.
ORCID: 0000-0001-6227-198X

Andrew M McIntosh (AM)

Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
ORCID: 0000-0002-0198-4588

Andrew McQuillin (A)

Division of Psychiatry, University College London, London, UK.
ORCID: 0000-0003-1567-2240

Derek W Morris (DW)

Centre for Neuroimaging, Cognition and Genomics, Discipline of Biochemistry, National University of Ireland Galway, Galway, Ireland.
ORCID: 0000-0002-3413-570X

Michael C O'Donovan (MC)

MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
ORCID: 0000-0001-7073-2379

Roel A Ophoff (RA)

Department of Psychiatry and Biobehavioral Science, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Department of Psychiatry, Erasmus Medical Center, Erasmus University, Rotterdam, the Netherlands.
ORCID: 0000-0002-8287-6457

Michael J Owen (MJ)

MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
ORCID: 0000-0003-4798-0862

Nancy L Pedersen (NL)

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Danielle Posthuma (D)

Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU Amsterdam, Amsterdam, the Netherlands.
ORCID: 0000-0001-7582-2365

Andreas Reif (A)

Department of Psychiatry, Psychosomatic Medicine and Psychiatry, University Hospital Frankfurt - Goethe University, Frankfurt, Germany.
ORCID: 0000-0002-0992-634X

Neil Risch (N)

Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.

Catherine Schaefer (C)

Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
ORCID: 0000-0003-2644-055X

Laura Scott (L)

Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
ORCID: 0000-0002-4886-5084

Tarjinder Singh (T)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
ORCID: 0000-0003-0601-6815

Jordan W Smoller (JW)

Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0002-0381-6334

Matthew Solomonson (M)

Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

David St Clair (DS)

Institute for Medical Sciences, University of Aberdeen, Aberdeen, UK.

Eli A Stahl (EA)

Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Annabel Vreeker (A)

Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC Sophia Children Hospital, Erasmus University, Rotterdam, the Netherlands.

James T R Walters (JTR)

MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
ORCID: 0000-0002-6980-4053

Weiqing Wang (W)

Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
ORCID: 0000-0003-1565-0148

Nicholas A Watts (NA)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Robert Yolken (R)

Stanley Division of Developmental Neurovirology, Johns Hopkins University, Baltimore, MD, USA.

Peter P Zandi (PP)

Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.
ORCID: 0000-0001-8423-2623

Benjamin M Neale (BM)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. bneale@broadinstitute.org.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA. bneale@broadinstitute.org.
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. bneale@broadinstitute.org.
ORCID: 0000-0003-1513-6077

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines adaptatrices de la transduction du signal › Protéines d'ancrage aux protéines kinases A › Exome sequencing in bipolar disorder...
questionsmedicales.fr › Troubles mentaux › Troubles de l'humeur › Troubles bipolaires et apparentés › Trouble bipolaire › Exome sequencing in bipolar disorder...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Exome › Exome sequencing in bipolar disorder...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › Exome sequencing in bipolar disorder...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Exome sequencing in bipolar disorder...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Exome sequencing in bipolar disorder...
questionsmedicales.fr › Troubles mentaux › Schizophrénie et troubles avec traits psychotiques › Schizophrénie › Exome sequencing in bipolar disorder...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ADN › Séquençage du génome entier › Séquençage de l'exome › Exome sequencing in bipolar disorder...