New findings in the genetics of major psychoses
- PMID: 20373670
- PMCID: PMC3181946
- DOI: 10.31887/DCNS.2010.12.1/mnoethen
New findings in the genetics of major psychoses
Abstract
Schizophrenia and bipolar disorder have a largely unknown pathophysiology and etiology, but they are highly heritable. Although linkage and association studies have identified a series of chromosomal regions likely to contain susceptibility genes, progress in identifying causative genes has been largely disappointing. However, rapid technological advances are beginning to lead to new insights. Systematic genome-wide association and follow-up studies have reported genome-wide significant association findings of common variants for schizophrenia and bipolar disorder. The risk conferred by individual variants is small, and some variants confer a risk for both disorders. In addition, recent studies have identified rare, large structural variants (copy number variants) that confer a greater risk for schizophrenia. This review summarizes recent developments in genetic research into schizophrenia and bipolar disorder, and discusses possible future directions in this field.
La esquizofrenia y el trastorno bipolar tienen una etiología y una fisiopatología en gran medida desconocidas, pero son altamente heredables. Aunque los estudios de ligamiento y de asociación han identificado una serie de regiones cromosómicas que contienen probablemente genes susceptibles, el progreso en la identificación de genes causales ha sido muy decepcionante. Sin embargo, los rápidos avances tecnológicos están dando origen a nuevos conocimientos. Los estudios sistemáticos de asociación del genoma completo y de seguimiento han informado acerca de hallazgos de asociación significativa del genoma completo y variantes comunes para la esquizofrenia y el trastorno bipolar. El riesgo que determinan las variantes individuales es pequeño y algunas de ellas confieren un riesgo para ambos trastornos. Además, estudios recientes han identificado variantes estructurales largas y raras (variantes de número de copias) que otorgan un mayor riego para la esquizofrenia. Esta revisión resume los desarrollos recientes en la investigación genética de la esquizofrenia y del trastorno bipolar y discute las posibles direcciones futuras en este campo.
La physiopathologie et l'étiologie de la schizophrénie et des troubles bipolaires restent largement méconnues mais fortement héréditaires. Des études de liaison et d'association ont identifié des séries de régions chromosomiques contenant probablement des gènes de susceptibilité, mais l'identification des gènes de causalité est extrêmement décevante. Des avancées technologiques rapides commencent cependant à voir le jour. Des études systématiques d'association sur le génome entier et de suivi ont découvert une association significative au niveau du génome entier de variants communs pour la schizophrénie et les troubles bipolaires. Le risque inhérent aux variants individuels est faible, et certains variants comportent un risque pour les deux pathologies. De plus, des études récentes ont identifié des variants structurels importants et rares (CNV = copy number variants, variants du nombre de copies) liés à un risque plus élevé de schizophrénie. Cet article résume les avancées récentes de la recherche génétique concernant la schizophrénie et les troubles bipolaires et analyse les perspectives possibles dans ce domaine.
Similar articles
-
Searching genetic risk factors for schizophrenia and bipolar disorder: learn from the past and back to the future.Hum Mutat. 2009 Aug;30(8):1139-52. doi: 10.1002/humu.21042. Hum Mutat. 2009. PMID: 19626716 Review.
-
Genome-wide searches for bipolar disorder genes.Curr Psychiatry Rep. 2011 Dec;13(6):522-7. doi: 10.1007/s11920-011-0226-y. Curr Psychiatry Rep. 2011. PMID: 21837483
-
Genetic analysis of schizophrenia and bipolar disorder reveals polygenicity but also suggests new directions for molecular interrogation.Curr Opin Neurobiol. 2015 Feb;30:131-8. doi: 10.1016/j.conb.2014.12.001. Epub 2014 Dec 24. Curr Opin Neurobiol. 2015. PMID: 25544106 Review.
-
Chromosome abnormalities, mental retardation and the search for genes in bipolar disorder and schizophrenia.Neurotox Res. 2008 Oct;14(2-3):113-20. doi: 10.1007/BF03033803. Neurotox Res. 2008. PMID: 19073419 Review.
-
After GWAS: searching for genetic risk for schizophrenia and bipolar disorder.Am J Psychiatry. 2011 Mar;168(3):253-6. doi: 10.1176/appi.ajp.2010.10091340. Epub 2011 Feb 1. Am J Psychiatry. 2011. PMID: 21285144 Free PMC article. Review.
Cited by
-
Genome-wide methylome analyses reveal novel epigenetic regulation patterns in schizophrenia and bipolar disorder.Biomed Res Int. 2015;2015:201587. doi: 10.1155/2015/201587. Epub 2015 Feb 4. Biomed Res Int. 2015. PMID: 25734057 Free PMC article.
-
The Splice Is Right: ANK3 and the Control of Cortical Circuits.Biol Psychiatry. 2016 Aug 15;80(4):263-265. doi: 10.1016/j.biopsych.2016.06.006. Biol Psychiatry. 2016. PMID: 27468628 Free PMC article. No abstract available.
-
Genetic Polymorphisms in miR-137 and Its Target Genes, TCF4 and CACNA1C, Contribute to the Risk of Bipolar Disorder: A Preliminary Case-Control Study and Bioinformatics Analysis.Dis Markers. 2022 Sep 22;2022:1886658. doi: 10.1155/2022/1886658. eCollection 2022. Dis Markers. 2022. PMID: 36193501 Free PMC article.
-
The DNA methylome and transcriptome of different brain regions in schizophrenia and bipolar disorder.PLoS One. 2014 Apr 28;9(4):e95875. doi: 10.1371/journal.pone.0095875. eCollection 2014. PLoS One. 2014. PMID: 24776767 Free PMC article.
-
Genetic risk of clozapine-induced leukopenia and neutropenia: a genome-wide association study.Transl Psychiatry. 2021 Jun 3;11(1):343. doi: 10.1038/s41398-021-01470-z. Transl Psychiatry. 2021. PMID: 34083506 Free PMC article.
References
-
- Sullivan PF, Kendler KS, Neale MC. Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Arch Gen Psychiatry. 2003;60:1187–1192. - PubMed
-
- Craddock N, Forty L. Genetics of affective (mood) disorders. Eur J Hum Genet. 2006;14:660–668. - PubMed
-
- Gottesman, II, Hanson DR. Human development: biological and genetic processes. Annu Rev Psychol. 2005;56:263–286. - PubMed
-
- Kato T, Kuratomi G, Kato N. Genetics of bipolar disorder. Drugs Today (Barc) 2005;41:335–344. - PubMed
-
- Hattori E, Liu C, Zhu H, Gershon ES. Genetic tests of biologic systems in affective disorders. Mol Psychiatry. 2005;10:719–740. - PubMed
Publication types
MeSH terms
LinkOut - more resources
Full Text Sources
Medical