Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Typ-2-Diabetes und Adipositas Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende

Die Highlights vom Kongress des American College of Cardiology 2024

Im April diskutierten die Herz-Kreislauf-Spezialisten aus der ganzen Welt auf dem  Kongress des American College of Cardiology (ACC) u.a. neue Therapieansätze bei akutem Myokardinfarkt, koronarer Herzerkrankung, kardiogenem Schock oder Aortenklappenstenose. In unserem Kongress-Dossier haben wir für Sie Berichte über die „Late-Breaking Trials“ und andere wichtige Studien zusammengestellt. 
Erweiterte Suche
Anmelden
nach oben
Current Neurology and Neuroscience Reports
Erschienen in: Current Neurology and Neuroscience Reports 3/2012

01.06.2012 | Genetics (V Bonifati, Section Editor)

Schizophrenia Genetics: Putting All the Pieces Together

verfasst von: Simon L. Girard, Patrick A. Dion, Guy A. Rouleau

Erschienen in: Current Neurology and Neuroscience Reports | Ausgabe 3/2012

Einloggen, um Zugang zu erhalten

Abstract

Schizophrenia is a major mental disorder characterized by a deep disruption of the thinking process and of emotional response. For many decades, genetics studies have yielded little success in identifying genetic factors responsible for the disease. However, with the recent breakthroughs in genome analysis technologies, the field of the genetics of schizophrenia has progressed a lot in the last years. Both common and rare variants have been successfully associated with the disease and a particular emphasis has been made on rare copy number variations. Recently, a new paradigm linking de novo mutations to the genetic mechanism of schizophrenia has been unravelled. The aim of this review is to discuss the most important genetic studies made in the field to give a general perspective of where to go in the future.
Literatur
1.
2.
Tienari P. Schizophrenia in Finnish male twins. In: Lader MH, editor. Studies of schizophrenia. 1975. pp. 29–35.
3.
Fischer M, Harvald B, Hauge M. A Danish twin study of schizophrenia. Br J Psychiatry. 1969;115(526):981–90.PubMedCrossRef
4.
Kendler KS, Robinette CD. Schizophrenia in the National Academy of Sciences-National Research Council Twin Registry: a 16-year update. Am J Psychiatry. 1983;140(12):1551–63.PubMed
5.
Onstad S, Skre I, Torgersen S, Kringlen E. Twin concordance for DSM-III-R schizophrenia. Acta Psychiatr Scand. 1991;83(5):395–401.PubMedCrossRef
6.
Cannon TD, Kaprio J, Lönnqvist J, Huttunen M, Koskenvuo M. The genetic epidemiology of schizophrenia in a Finnish twin cohort. A population-based modeling study. Arch Gen Psychiatry. 1998;55(1):67–74.PubMedCrossRef
7.
Cardno AG, Marshall EJ, Coid B, et al. Heritability estimates for psychotic disorders: the Maudsley twin psychosis series. Arch Gen Psychiatry. 1999;56(2):162–8.PubMedCrossRef
8.
Sullivan PF, Kendler KS, Neale MC. Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Arch Gen Psychiatry. 2003;60(12):1187–92.PubMedCrossRef
9.
10.
Pulver AE, Karayiorgou M, Wolyniec PS, et al. Sequential strategy to identify a susceptibility gene for schizophrenia: report of potential linkage on chromosome 22q12-q13.1: part 1. Am J Med Genet. 1994;54(1):36–43.PubMedCrossRef
11.
Stefansson H, Sigurdsson E, Steinthorsdottir V, et al. Neuregulin 1 and susceptibility to schizophrenia. Am J Hum Genet. 2002;71(4):877–92.PubMedCrossRef
12.
Petryshen TL, Middleton FA, Kirby A, et al. Support for involvement of neuregulin 1 in schizophrenia pathophysiology. Mol Psychiatry. 2005;10(4):366–74. 328.PubMedCrossRef
13.
Seshadri S, Kamiya A, Yokota Y, et al. Disrupted-in-Schizophrenia-1 expression is regulated by beta-site amyloid precursor protein cleaving enzyme-1-neuregulin cascade. Proc Natl Acad Sci U S A. 2010;107(12):5622–7.PubMedCrossRef
14.
Bray NJ, Preece A, Williams NM, et al. Haplotypes at the dystrobrevin binding protein 1 (DTNBP1) gene locus mediate risk for schizophrenia through reduced DTNBP1 expression. Hum Mol Genet. 2005;14(14):1947–54.PubMedCrossRef
15.
Blackwood DH, Fordyce A, Walker MT, et al. Schizophrenia and affective disorders–cosegregation with a translocation at chromosome 1q42 that directly disrupts brain-expressed genes: clinical and P300 findings in a family. Am J Hum Genet. 2001;69(2):428–33.PubMedCrossRef
16.
Millar JK, Wilson-Annan JC, Anderson S, et al. Disruption of two novel genes by a translocation co-segregating with schizophrenia. Hum Mol Genet. 2000;9(9):1415–23.PubMedCrossRef
17.
Brandon NJ, Millar JK, Korth C, et al. Understanding the role of DISC1 in psychiatric disease and during normal development. J Neurosci. 2009;29(41):12768–75.PubMedCrossRef
18.
Betcheva ET, Mushiroda T, Takahashi A, et al. Case–control association study of 59 candidate genes reveals the DRD2 SNP rs6277 (C957T) as the only susceptibility factor for schizophrenia in the Bulgarian population. J Hum Genet. 2009;54(2):98–107.PubMedCrossRef
19.
Shifman S, Johannesson M, Bronstein M, et al. Genome-wide association identifies a common variant in the reelin gene that increases the risk of schizophrenia only in women. PLoS Genet. 2008;4(2):e28.PubMedCrossRef
20.
Kirov G, Zaharieva I, Georgieva L, et al. A genome-wide association study in 574 schizophrenia trios using DNA pooling. Mol Psychiatry. 2009;14(8):796–803.PubMedCrossRef
21.
Sullivan PF, Lin D, Tzeng JY, et al. Genomewide association for schizophrenia in the CATIE study: results of stage 1. Mol Psychiatry. 2008;13(6):570–84.PubMedCrossRef
22.
O’Donovan MC, Craddock N, Norton N, et al. Identification of loci associated with schizophrenia by genome-wide association and follow-up. Nat Genet. 2008;40(9):1053–5.PubMedCrossRef
23.
Steinberg S, Mors O, Borglum AD, et al. Expanding the range of ZNF804A variants conferring risk of psychosis. Mol Psychiatry. 2010;16(1):59–66.
24.
Riley B, Thiselton D, Maher BS, et al. Replication of association between schizophrenia and ZNF804A in the Irish Case–control Study of Schizophrenia sample. Mol Psychiatry. 2010;15(1):29–37.PubMedCrossRef
25.
Hill MJ, Jeffries AR, Dobson RJB, Price J, Bray NJ. Knockdown of the psychosis susceptibility gene ZNF804A alters expression of genes involved in cell adhesion. Hum Mol Genet. 2011;21(5):1018–24.
26.
• Stefansson H, Ophoff RA, Steinberg S, et al. Common variants conferring risk of schizophrenia. Nature. 2009;460(7256):744–7. This is one of the first GWAS that identified the MHC as an associated region.PubMed
27.
• Purcell SM, Wray NR, Stone JL, et al. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature. 2009;460(7256):748–52. This is one of the first GWAS that identified the MHC as an associated region.PubMed
28.
Handel AE, Ramagopalan SV. The potential role of major histocompatibility complex class I in schizophrenia. Biol Psychiatry. 2010;68(7):e29–30. author reply e31.PubMedCrossRef
29.
Shi Y, Li Z, Xu Q, et al. Common variants on 8p12 and 1q24.2 confer risk of schizophrenia. Nat Genet. 2011;43(12):1224–7.PubMedCrossRef
30.
Yue W-H, Wang H-F, Sun L-D, et al. Genome-wide association study identifies a susceptibility locus for schizophrenia in Han Chinese at 11p11.2. Nat Genet. 2011;43(12):1228–31.PubMedCrossRef
31.
•• Ripke S, Sanders AR, Kendler KS, et al. Genome-wide association study identifies five new schizophrenia loci. Nat Genet. 2011;43(10):969–76. This is the largest GWAS made on a SCZ cohort. It identifies MIR137 as an associated locus.PubMedCrossRef
32.
Balaguer F, Link A, Lozano JJ, et al. Epigenetic silencing of miR-137 is an early event in colorectal carcinogenesis. Cancer Res. 2010;70(16):6609–18.PubMedCrossRef
33.
Liu M, Lang N, Qiu M, et al. miR-137 targets Cdc42 expression, induces cell cycle G1 arrest and inhibits invasion in colorectal cancer cells. Int J Cancer. 2011;128(6):1269–79.PubMedCrossRef
34.
Silber J, Lim DA, Petritsch C, et al. miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells. BMC Med. 2008;6:14.PubMedCrossRef
35.
Tarantino C, Paolella G, Cozzuto L, et al. miRNA 34a, 100, and 137 modulate differentiation of mouse embryonic stem cells. FASEB J. 2010;24(9):3255–63.PubMedCrossRef
36.
• Walsh T, McClellan JM, McCarthy SE, et al. Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science. 2008;320(5875):539–43. This is one of the most important genome-wide CNV studies made in the field of SCZ.PubMedCrossRef
37.
Xu B, Roos JL, Levy S, et al. Strong association of de novo copy number mutations with sporadic schizophrenia. Nat Genet. 2008;40(7):880–5.PubMedCrossRef
38.
Anon. Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature. 2008;455(7210):237–41.CrossRef
39.
• Stefansson H, Rujescu D, Cichon S, et al. Large recurrent microdeletions associated with schizophrenia. Nature. 2008;455(7210):232–6. This is one of the most important genome-wide CNV study made in the field of SCZ.PubMedCrossRef
40.
Mulle JG, Dodd AF, McGrath JA, et al. Microdeletions of 3q29 confer high risk for schizophrenia. Am J Hum Genet. 2010;87(2):229–36.PubMedCrossRef
41.
McCarthy SE, Makarov V, Kirov G, et al. Microduplications of 16p11.2 are associated with schizophrenia. Nat Genet. 2009;41(11):1223–7.PubMedCrossRef
42.
Ingason A, Rujescu D, Cichon S, et al. Copy number variations of chromosome 16p13.1 region associated with schizophrenia. Mol Psychiatry. 2009;16(1):17–25.
43.
•• Craddock N, Hurles ME, Cardin N, et al. Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls. Nature. 2010;464(7289):713–20. This study made by the WTCCC shows that the common CNVs are unlikely to contribute significantly to disease as they are already tagged by the SNPs.PubMedCrossRef
44.
Malhotra D, McCarthy S, Michaelson JJ, et al. High frequencies of de novo CNVs in bipolar disorder and schizophrenia. Neuron. 2011;72(6):951–63.PubMedCrossRef
45.
• Gauthier J, Champagne N, Lafreniere RG, et al. De novo mutations in the gene encoding the synaptic scaffolding protein SHANK3 in patients ascertained for schizophrenia. Proc Natl Acad Sci U S A. 2010;107(17):7863–8. This is the first study to report a de novo mutation in a gene and to associate this gene with the disease.PubMedCrossRef
46.
Tarabeux J, Champagne N, Brustein E, et al. De novo truncating mutation in Kinesin 17 associated with schizophrenia. Biol Psychiatry. 2010;68(7):649–56.PubMedCrossRef
47.
Gauthier J, Siddiqui TJ, Huashan P, et al. Truncating mutations in NRXN2 and NRXN1 in autism spectrum disorders and schizophrenia. Hum Genet. 2011;130(4):563–73.
48.
• Awadalla P, Gauthier J, Myers RA, et al. Direct measure of the de novo mutation rate in autism and schizophrenia cohorts. Am J Hum Genet. 2010;87(3):316–24. This study has shown that the de novo mutation rate is higher than expected in SCZ.PubMedCrossRef
49.
•• Girard SL, Gauthier J, Noreau A, et al. Increased exonic de novo mutation rate in individuals with schizophrenia. Nat Genet. 2011;43(9):860–3. This study has shown a higher than expected rate of de novo mutation as well as identified a strong enrichment in de novo truncating mutations.PubMedCrossRef
50.
•• Xu B, Roos JL, Dexheimer P, et al. Exome sequencing supports a de novo mutational paradigm for schizophrenia. Nat Genet. 2011;43(9):864–8. This study has shown a higher than expected rate of de novo mutation as well as identified a strong enrichment in nonsynonymous mutations.PubMedCrossRef
51.
O’Roak BJ, Deriziotis P, Lee C, et al. Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations. Nat Genet. 2011;43(6):585–9.PubMedCrossRef
52.
Vissers LE, de Ligt J, Gilissen C, et al. A de novo paradigm for mental retardation. Nat Genet. 2010;42(12):1109–12.PubMedCrossRef
Metadaten
Titel
Schizophrenia Genetics: Putting All the Pieces Together
verfasst von
Simon L. Girard
Patrick A. Dion
Guy A. Rouleau
Publikationsdatum
01.06.2012
Verlag
Current Science Inc.
Erschienen in
Current Neurology and Neuroscience Reports / Ausgabe 3/2012
Print ISSN: 1528-4042
Elektronische ISSN: 1534-6293
DOI
https://doi.org/10.1007/s11910-012-0266-7

Weitere Artikel der Ausgabe 3/2012

Current Neurology and Neuroscience Reports 3/2012 Zur Ausgabe

Neuro-Oncology (LE Abrey, Section Editor)

Radiation Necrosis: Relevance with Respect to Treatment of Primary and Secondary Brain Tumors

Genetics (V Bonifati, Section Editor)

Recent Advances in the Genetics of the ALS-FTLD Complex

Genetics (V Bonifati, Section Editor)

Modeling Parkinson’s Disease Using Induced Pluripotent Stem Cells

Neuro-Ophthalmology (G Plant, Section Editor)

Papilledema: Are We Any Nearer to a Consensus on Pathogenesis and Treatment?

Neuro-Ophthalmology (G Plant, Section Editor)

Thyroid Eye Disease: Towards an Evidence Base for Treatment in the 21st Century

Neuro-Oncology (LE Abrey, Section Editor)

Temozolomide Dosing Regimens for Glioma Patients

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

Thrombektomie auch bei großen Infarkten von Vorteil

16.05.2024 Ischämischer Schlaganfall Nachrichten

Auch ein sehr ausgedehnter ischämischer Schlaganfall scheint an sich kein Grund zu sein, von einer mechanischen Thrombektomie abzusehen. Dafür spricht die LASTE-Studie, an der Patienten und Patientinnen mit einem ASPECTS von maximal 5 beteiligt waren.

Schwindelursache: Massagepistole lässt Otholiten tanzen

14.05.2024 Benigner Lagerungsschwindel Nachrichten

Wenn jüngere Menschen über ständig rezidivierenden Lagerungsschwindel klagen, könnte eine Massagepistole der Auslöser sein. In JAMA Otolaryngology warnt ein Team vor der Anwendung hochpotenter Geräte im Bereich des Nackens.

Schützt Olivenöl vor dem Tod durch Demenz?

10.05.2024 Morbus Alzheimer Nachrichten

Konsumieren Menschen täglich 7 Gramm Olivenöl, ist ihr Risiko, an einer Demenz zu sterben, um mehr als ein Viertel reduziert – und dies weitgehend unabhängig von ihrer sonstigen Ernährung. Dafür sprechen Auswertungen zweier großer US-Studien.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen
Bildnachweise