Genetics of schizophrenia

Current Opinion in Behavioral Sciences

Volumn 2, Issue , 2015, Pages 8-14

  Rees, Elliott ^a   O'Donovan, Michael C ^a   Owen, Michael J ^a  

^a CARDIFF UNIVERSITY   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ALLELE; COPY NUMBER VARIATION; DE NOVO MUTATION; GENETIC VARIABILITY; GENETICS; HUMAN; INDEL MUTATION; REVIEW; SCHIZOPHRENIA; SINGLE NUCLEOTIDE POLYMORPHISM;

EID: 84922648008     PISSN: None     EISSN: 23521546     Source Type: Journal    
DOI: 10.1016/j.cobeha.2014.07.001     Document Type: Review

References (55)

1. Gottesman I.I. Schizophrenia Genesis: The Origins of Madness 1991, Henry Holt & Company Inc New York.
2. Sullivan P.F., Kendler K.S., Neale M.C. Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Arch Gen Psychiatry 2003, 60:1187-1192.
3. Veltman J.A., Brunner H.G. De novo mutations in human genetic disease. Nat Rev Genet 2012, 13:565-575.
4. Kong A., Frigge M.L., Masson G., Besenbacher S., Sulem P., Magnusson G., Gudjonsson S.A., Sigurdsson A., Jonasdottir A., Jonasdottir A., et al. Rate of de novo mutations and the importance of father's age to disease risk. Nature 2012, 488:471-475.
5. McGrath J.J., Petersen L., Agerbo E., Mors O., Mortensen P., Pedersen C. A comprehensive assessment of parental age and psychiatric disorders. JAMA Psychiatry 2014, 71:301-309.
6. Kirov G., Pocklington A.J., Holmans P., Ivanov D., Ikeda M., Ruderfer D., Moran J., Chambert K., Toncheva D., Georgieva L., et al. De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia. Mol Psychiatry 2012, 17:142-153.
7. Malhotra D., McCarthy S., Michaelson Jacob J., Vacic V., Burdick Katherine E., Yoon S., Cichon S., Corvin A., Gary S., Gershon Elliot S., et al. High frequencies of de novo CNVs in bipolar disorder and schizophrenia. Neuron 2011, 72:951-963.
8. Xu B., Roos J.L., Levy S., van Rensburg E.J., Gogos J.A., Karayiorgou M. Strong association of de novo copy number mutations with sporadic schizophrenia. Nat Genet 2008, 40:880-885.
9. Sanders S.J., Ercan-Sencicek A.G., Hus V., Luo R., Murtha M.T., Moreno-De-Luca D., Chu S.H., Moreau M.P., Gupta A.R., Thomson S.A., et al. Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams Syndrome region, are strongly associated with autism. Neuron 2011, 70:863-885.
10. Rees E., Moskvina V., Owen M.J., O'Donovan M.C., Kirov G. De novo rates and selection of schizophrenia-associated copy number variants. Biol Psychiatry 2011, 70:1109-1114.
11. Fromer M., Pocklington A.J., Kavanagh D.H., Williams H.J., Dwyer S., Gormley P., Georgieva L., Rees E., Palta P., Ruderfer D.M., et al. De novo mutations in schizophrenia implicate synaptic networks. Nature 2014, 506:179-184.
12. McCarthy S., Gillis J., Kramer M., Lihm J., Yoon S., Berstein Y., Mistry M., Pavlidis P., Solomon R., Ghiban E. De novo mutations in schizophrenia implicate chromatin remodeling and support a genetic overlap with autism and intellectual disability. Mol Psychiatry 2014, 19:652-658.
13. Xu B., Ionita-Laza I., Roos J.L., Boone B., Woodrick S., Sun Y., Levy S., Gogos J.A., Karayiorgou M. De novo gene mutations highlight patterns of genetic and neural complexity in schizophrenia. Nat Genet 2012, 44:1365-1369.
14. Gulsuner S., Walsh T., Watts A.C., Lee M.K., Thornton A.M., Casadei S., Rippey C., Shahin H., Nimgaonkar V.L., Go R.C.P., et al. Spatial and temporal mapping of de novo mutations in schizophrenia to a fetal prefrontal cortical network. Cell 2013, 154:518-529.
15. Takata A., Xu B., Ionita-Laza I., Roos J.L., Gogos Joseph A., Karayiorgou M. Loss-of-function variants in schizophrenia risk and SETD1A as a candidate susceptibility gene. Neuron 2014, 82:773-780.
16. Iossifov I., Ronemus M., Levy D., Wang Z., Hakker I., Rosenbaum J., Yamrom B., Lee Y.-h., Narzisi G., Leotta A., et al. De Novo gene disruptions in children on the autistic spectrum. Neuron 2012, 74:285-299.
17. International Schizophrenia Consortium (ISC) Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature 2008, 455:237-241.
18. Kirov G., Grozeva D., Norton N., Ivanov D., Mantripragada K.K., Holmans P., International Schizophrenia Consortium, the Wellcome Trust Case Control Consortium, Craddock N., Owen M.J., O'Donovan M.C. Support for the involvement of large CNVs in the pathogenesis of schizophrenia. Hum Mol Genet 2009, 18:1497-1503.
19. Rees E., Walters J.T.R., Chambert K.D., Isles A.R., Chambert K.D., O'Dushlaine C., Szatkiewicz J., Richards A.L., Mahoney-Davies G., Georgieva L., et al. CNV analysis in a large schizophrenia sample implicates deletions at 16p12.1 and SLC1A1 and duplications at 1p36.33 and CGNL1. Hum Mol Genet 2014, 23:1669-1676.
20. Szatkiewicz J.P., O'Dushlaine C., Chen G., Chambert K., Moran J.L., Neale B.M., Fromer M., Ruderfer D., Akterin S., Bergen S.E., et al. Copy number variation in schizophrenia in Sweden. Mol Psychiatry 2014, 19:762-773.
21. Karayiorgou M., Morris M.A., Morrow B., Shprintzen R.J., Goldberg R., Borrow J., Gos A., Nestadt G., Wolyniec P.S., Lasseter V.K. Schizophrenia susceptibility associated with interstitial deletions of chromosome 22q11. Proc Natl Acad Sci U S A 1995, 92:7612-7616.
22. Murphy K.C., Jones L.A., Owen M.J. High rates of schizophrenia in adults with velo-cardio-facial syndrome. Arch Gen Psychiatry 1999, 56:940-945.
23. Morris D.W., Pearson R.D., Cormican P., Kenny E.M., O'Dushlaine C.T., Perreault L-PL, Giannoulatou E., Tropea D., Maher B.S., Wormley B., et al. An inherited duplication at the gene p21 Protein-Activated Kinase 7 (PAK7) is a risk factor for psychosis. Hum Mol Genet 2014, 23:3316-3326.
24. Rees E., Walters J.T.R., Georgieva L., Isles A.R., Chambert K.D., Richards A.L., Mahoney-Davies G., Legge S.E., Moran J.L., McCarroll S.A., et al. Analysis of copy number variations at 15 schizophrenia-associated loci. Br J Psychiatry 2014, 204:108-114.
25. Robinson M.R., Wray N.R., Visscher P.M. Explaining additional genetic variation in complex traits. Trends Genet 2014, 30:124-132.
26. Lupski J.R. Genomic disorders: structural features of the genome can lead to DNA rearrangements and human disease traits. Trends Genet 1998, 14:417-422.
27. Südhof T.C. Neuroligins and neurexins link synaptic function to cognitive disease. Nature 2008, 455:903-911.
28. Kirov G., Rees E., Walters T.J., Escott-Price V., Georgieva L., Richards A.L., Chambert K.D., Davies G., Legge S.E., Moran J.L., et al. The penetrance of copy number variations for schizophrenia and developmental delay. Biol Psychiatry 2014, 75:378-385.
29. Malhotra D., Sebat J. CNVs: Harbingers of a rare variant revolution in psychiatric genetics. Cell 2012, 148:1223-1241.
30. Glessner J.T., Wang K., Cai G., Korvatska O., Kim C.E., Wood S., Zhang H., Estes A., Brune C.W., Bradfield J.P., et al. Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. Nature 2009, 459:569-573.
31. de Kovel C.G.F., Trucks H., Helbig I., Mefford H.C., Baker C., Leu C., Kluck C., Muhle H., von Spiczak S., Ostertag P., et al. Recurrent microdeletions at 15q11.2 and 16p13.11 predispose to idiopathic generalized epilepsies. Brain 2010, 133:23-32.
32. Helbig I., Mefford H.C., Sharp A.J., Guipponi M., Fichera M., Franke A., Muhle H., de Kovel C., Baker C., von Spiczak S., et al. 15q13.3 microdeletions increase risk of idiopathic generalized epilepsy. Nat Genet 2009, 41:160-162.
33. Williams N.M., Zaharieva I., Martin A., Langley K., Mantripragada K., Fossdal R., Stefansson H., Stefansson K., Magnusson P., Gudmundsson O.O., et al. Rare chromosomal deletions and duplications in attention-deficit hyperactivity disorder: a genome-wide analysis. Lancet 2010, 376:1401-1408.
34. Girirajan S., Rosenfeld J.A., Coe B.P., Parikh S., Friedman N., Goldstein A., Filipink R.A., McConnell J.S., Angle B., Meschino W.S., et al. Phenotypic heterogeneity of genomic disorders and rare copy-number variants. N Engl J Med 2012, 367:1321-1331.
35. Kaminsky E.B., Kaul V., Paschall J., Church D.M., Bunke B., Kunig D., Moreno-De-Luca D., Moreno-De-Luca A., Mulle J.G., Warren S.T., et al. An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabilities. Genet Med 2011, 13:777-784.
36. Girirajan S., Eichler E.E. Phenotypic variability and genetic susceptibility to genomic disorders. Hum Mol Genet 2010, 19:R176-R187.
37. Jacquemont S., Reymond A., Zufferey F., Harewood L., Walters R.G., Kutalik Z., Martinet D., Shen Y., Valsesia A., Beckmann N.D., et al. Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus. Nature 2011, 478:97-102.
38. Rees E., Kirov G., Sanders A., Walters J.T.R., Chambert K.D., Shi J., Szatkiewicz J., O'Dushlaine C., Richards A.L., Green E.K., et al. Evidence that duplications of 22q11.2 protect against schizophrenia. Mol Psychiatry 2014, 19:37-40.
39. Stefansson H., Meyer-Lindenberg A., Steinberg S., Magnusdottir B., Morgen K., Arnarsdottir S., Bjornsdottir G., Walters G.B., Jonsdottir G.A., Doyle O.M. CNVs conferring risk of autism or schizophrenia affect cognition in controls. Nature 2014, 505:361-366.
40. Crowley J.J., Hilliard C.E., Kim Y., Morgan M.B., Lewis L.R., Muzny D.M., Hawes A.C., Sabo A., Wheeler D.A., Lieberman J.A., et al. Deep resequencing and association analysis of schizophrenia candidate genes. Mol Psychiatry 2013, 18:138-140.
41. Need Anna C., McEvoy Joseph P., Gennarelli M., Heinzen Erin L., Ge D., Maia Jessica M., Shianna Kevin V., He M., Cirulli Elizabeth T., Gumbs Curtis E., et al. Exome sequencing followed by large-scale genotyping suggests a limited role for moderately rare risk factors of strong effect in schizophrenia. Am J Hum Genet 2012, 91:303-312.
42. Purcell S.M., Moran J.L., Fromer M., Ruderfer D., Solovieff N., Roussos P., O'Dushlaine C., Chambert K., Bergen S.E., Kähler A., et al. A polygenic burden of rare disruptive mutations in schizophrenia. Nature 2014, 506:185-190.
43. Ripke S., O'Dushlaine C., Chambert K., Moran J.L., Kahler A.K., Akterin S., Bergen S.E., Collins A.L., Crowley J.J., Fromer M., et al. Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Nat Genet 2013, 45:1150-1159.
44. Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium Genome-wide association study identifies five new schizophrenia loci. Nat Genet 2011, 43:969-976.
45. Schizophrenia Working Group of the Psychiatric Genomics Consortium Biological insights from 108 schizophrenia-associated genetic loci. Nature 2014, 511:421-427.
46. International Schizophrenia Consortium, Purcell S.M., Wray N.R., Stone J.L., Visscher P.M., O'Donovan M.C., Sullivan P.F., Sklar P. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 2009, 460:748-752.
47. Lee S.H., DeCandia T.R., Ripke S., Yang J., PGC-SCZ, ISC, MGS, Sullivan P.F., Goddard M.E., Keller M.C., et al. Estimating the proportion of variation in susceptibility to schizophrenia captured by common SNPs. Nat Genet 2012, 44:247-250.
48. Cross-Disorder Group of the Psychiatric Genomics Consortium Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nat Genet 2013, 45:984-994.
49. Psychiatric GWAS Consortium A framework for interpreting genome-wide association studies of psychiatric disorders. Mol Psychiatry 2009, 14:10-17.
50. Corvin A., Morris D.W. Genome-wide association studies: findings at the major histocompatibility complex locus in psychosis. Biol Psychiatry 2014, 75:276-283.
51. Cross-Disorder Group of the Psychiatric Genomics Consortium, Genetic Risk Outcome of Psychosis Consortium Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet 2013, 381:1371-1379.
52. O'Donovan M.C., Craddock N., Norton N., Williams H., Peirce T., Moskvina V., Nikolov I., Hamshere M., Carroll L., Georgieva L., et al. Identification of loci associated with schizophrenia by genome-wide association and follow-up. Nat Genet 2008, 40:1053-1055.
53. Ruderfer D.M., Fanous A.H., Ripke S., McQuillin A., Amdur R.L., Gejman P.V., O'Donovan M.C., Andreassen O.A., Djurovic S., Hultman C.M., et al. Polygenic dissection of diagnosis and clinical dimensions of bipolar disorder and schizophrenia. Mol Psychiatry 2013, 10.1038/mp.2013.1138.
54. Lencz T., Knowles E., Davies G., Guha S., Liewald D.C., Starr J.M., Djurovic S., Melle I., Sundet K., Christoforou A., et al. Molecular genetic evidence for overlap between general cognitive ability and risk for schizophrenia: a report from the Cognitive Genomics consorTium (COGENT). Mol Psychiatry 2013, 19:168-174.
55. Doherty J.L., Owen M.J. Genomic insights into the overlap between psychiatric disorders: implications for research and clinical practice. Genome Med 2014, 6:29. 10.1186/gm1546.