Schizophrenia genetics: Emerging themes for a complex disorder

Molecular Psychiatry

Volumn 20, Issue 1, 2015, Pages 72-76

  Kavanagh, D H ^a   Tansey, K E ^a   O'Donovan, M C ^a   Owen, M J ^a  

^a CARDIFF UNIVERSITY   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

AUTISM; BIPOLAR DISORDER; EXOME; GENE; GENE FREQUENCY; GENE SEQUENCE; GENETIC ASSOCIATION; GENETIC VARIABILITY; GENETICS; GENOTYPE; HIGH THROUGHPUT SEQUENCING; INTELLECTUAL IMPAIRMENT; MAJOR DEPRESSION; MENTAL DISEASE; PRIORITY JOURNAL; REVIEW; RISK; SCHIZOPHRENIA; COMPLICATION; GENETIC PREDISPOSITION; HUMAN; INTELLECTUAL DISABILITY;

BIPOLAR DISORDER; GENE FREQUENCY; GENETIC PREDISPOSITION TO DISEASE; GENETIC VARIATION; GENOME-WIDE ASSOCIATION STUDY; GENOTYPE; HUMANS; INTELLECTUAL DISABILITY; SCHIZOPHRENIA;

EID: 84922261486     PISSN: 13594184     EISSN: 14765578     Source Type: Journal    
DOI: 10.1038/mp.2014.148     Document Type: Review

References (54)

1. Owen MJ, ODonovan MC, Gottesman II. Schizophrenia In Psychiatric Genetics and Genomics. OUP Oxford: New Ed edition. 2002, pp 247-266.
2. ODonovan MC, Craddock N, Norton N, Williams H, Peirce T, Moskvina V et al. Identification of loci associated with schizophrenia by genome-wide association and follow-up. Nat Genet 2008; 40: 1053-1055.
3. Stefansson H, Ophoff RA, Steinberg S, Andreassen OA, Cichon S, Rujescu D et al. Common variants conferring risk of schizophrenia. Nature 2009; 460: 744-747.
4. Shi J, Levinson DF, Duan J, Sanders AR, Zheng Y, Pe'er I et al. Common variants on chromosome 6p22.1 are associated with schizophrenia. Nature 2009; 460: 753-757.
5. International Schizophrenia Consortium. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 2009; 460: 748-752.
6. Ikeda M, Aleksic B, Kinoshita Y, Okochi T, Kawashima K, Kushima I et al. Genomewide association study of schizophrenia in a Japanese population. Biol Psychiatry 2011; 69: 472-478.
7. Hamshere M L, Walters JT, Smith R, Richards AL, Green E, Grozeva D et al. Genome-wide significant associations in schizophrenia to ITIH3/4, CACNA1C and SDCCAG8, and extensive replication of associations reported by the Schizophrenia PGC. Mol Psychiatry 2012; 18: 708-71210.1038/mp.2012.67.
8. Genome-wide association study implicates HLA-C∗01. As a risk factor at the major histocompatibility complex locus in schizophrenia. Biol Psychiatry 2012; 72: 620-628.
9. Lencz T, Guha S, Liu C, Rosenfeld J, Mukherjee S, DeRosse P et al. Genome-wide association study implicates NDST3 in schizophrenia and bipolar disorder. Nat Commun 2013; 4: 2739.
10. Sullivan PF, Daly MJ, ODonovan M. Genetic architectures of psychiatric disorders: the emerging picture and its implications. Nat Rev Genet 2012; 13: 537-551.
11. Ripke S, O'Dushlaine C, Chambert K, Moran JL, Khler AK, Akterin S et al. Genomewide association analysis identifies 13 new risk loci for schizophrenia. Nat Genet 2013; 45: 1150-1159.
12. Green E K, Grozeva D, Jones I, Jones L, Kirov G, Caesar S et al. The bipolar disorder risk allele at CACNA1C also confers risk of recurrent major depression and of schizophrenia. Mol Psychiatry 2010; 15: 1016-1022.
13. Smoller JW et al. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet 2013; 381: 1371-1379.
14. Lee SH, Ripke S, Neale BM, Faraone SV, Purcell SM, Perlis RH, Mowry BJ et al. Genetic relationship between five psychiatric disorders estimated from genomewide SNPs. Nat Genet 2013; 45: 984-994.
15. Yang J, Lee SH, Goddard ME, Visscher PM. GCTA: a tool for genome-wide complex trait analysis. Am J Hum Genet 2011; 88: 76-82.
16. Karayiorgou M, Morris MA, Morrow B, Shprintzen RJ, Goldberg R, Borrow J et al. Schizophrenia susceptibility associated with interstitial deletions of chromosome 22q11. Proc Natl Acad Sci 1995; 92: 7612-7616.
17. Malhotra D, Sebat J. CNVs: harbingers of a rare variant revolution in psychiatric genetics. Cell 2012; 148: 1223-1241.
18. Xu B, Roos JL, Levy S, van Rensburg EJ, Gogos JA, Karayiorgou M et al. Strong association of de novo copy number mutations with sporadic schizophrenia. Nat Genet 2008; 40: 880-885.
19. Kirov G, Pocklington AJ, Holmans P, Ivanov D, Ikeda M, Ruderfer D et al. De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia. Mol Psychiatry 2012; 17: 142-153.
20. Rees E, Walters JT, Georgieva L, Isles AR, Chambert KD, Richards AL et al. Analysis of copy number variations at 15 schizophrenia-associated loci in a large, independent cohort. Br J Psychiatry 2013; 204: 108-114.
21. Szatkiewicz JP, O'Dushlaine C, Chen G, Chambert K, Moran JL, Neale BM et al. Copy number variation in schizophrenia in Sweden. Mol Psychiatry 2014; 19: 762-773.
22. Elia J, Glessner JT, Wang K, Takahashi N, Shtir CJ, Hadley D et al. Genome-wide copy number variation study associates metabotropic glutamate receptor gene networks with attention deficit hyperactivity disorder. Nat Genet 2012; 44: 78-84.
23. Cooper GM, Coe BP, Girirajan S, Rosenfeld JA, Vu TH, Baker C et al. A copy number variation morbidity map of developmental delay. Nat Genet 2011; 43: 838-846.
24. Williams NM, Franke B, Mick E, Anney RJ, Freitag CM, Gill M et al. Genome-wide analysis of copy number variants in attention deficit hyperactivity disorder: the role of rare variants and duplications at 15q13.3. Am J Psychiatry 2012; 169: 195-204.
25. Girirajan S, Eichler EE. Phenotypic variability and genetic susceptibility to genomic disorders. Hum Mol Genet 2010; 19: R176-R187.
26. Sahoo T, Theisen A, Rosenfeld JA, Lamb AN, Ravnan JB, Schultz RA et al. Copy number variants of schizophrenia susceptibility loci are associated with a spectrum of speech and developmental delays and behavior problems. Genet Med 2011; 13: 868-880.
27. Kirov G, Rees E, Walters JT, Escott-Price V, Georgieva L, Richards AL et al. The Penetrance of Copy Number Variations for Schizophrenia and Developmental Delay. Biol Psychiatry 2013; 75: 378-385.
28. Walsh T, McClellan JM, McCarthy SE, Addington AM, Pierce SB, Cooper GM et al. Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science 2008; 320: 539-543.
29. Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature 2014; 511: 421-427.
30. Hamshere ML, Walters JT, Smith R, Richards AL, Green E, Grozeva D et al. Genomewide significant associations in schizophrenia to ITIH3/4, CACNA1C and SDCCAG8, and extensive replication of associations reported by the Schizophrenia PGC. Mol Psychiatry 2013; 18: 708-712.
31. Plenge RM, Scolnick EM, Altshuler D. Validating therapeutic targets through human genetics. Nat Rev Drug Discov 2013; 12: 581-594.
32. ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature 2012; 489: 57-74.
33. Carter CS, Bullmore ET, Harrison P. Is there a flame in the brain in psychosis? Biol Psychiatry 2014; 75: 258-259.
34. Fromer M, Pocklington AJ, Kavanagh DH, Williams HJ, Dwyer S, Gormley P et al. De novo mutations in schizophrenia implicate synaptic networks. Nature 2014; 506: 179-184.
35. Purcell SM, Moran JL, Fromer M, Ruderfer D, Solovieff N, Roussos P et al. A polygenic burden of rare disruptive mutations in schizophrenia. Nature 2014; 506: 185-190.
36. Xu B, Ionita-Laza I, Roos JL, Boone B, Woodrick S, Sun Y et al. De novo gene mutations highlight patterns of genetic and neural complexity in schizophrenia. Nat Genet 2012; 44: 1365-1369.
37. Girard SL, Gauthier J, Noreau A, Xiong L, Zhou S, Jouan L et al. Increased exonic de novo mutation rate in individuals with schizophrenia. Nat Genet 2011; 43: 860-863.
38. Gulsuner S, Walsh T, Watts AC, Lee MK, Thornton AM, Casadei S et al. Spatial and temporal mapping of de novo mutations in schizophrenia to a fetal prefrontal cortical network. Cell 2013; 154: 518-529.
39. Neale BM, Kou Y, Liu L, Ma'ayan A, Samocha KE, Sabo A et al. Patterns and rates of exonic de novo mutations in autism spectrum disorders. Nature 2012; 485: 242-245.
40. ORoak BJ, Vives L, Girirajan S, Karakoc E, Krumm N, Coe BP et al. Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature 2012; 485: 246-250.
41. Sanders SJ, Murtha MT, Gupta AR, Murdoch JD, Raubeson MJ, Willsey AJ et al. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature 2012; 485: 237-241.
42. Iossifov I, Ronemus M, Levy D, Wang Z, Hakker I, Rosenbaum J et al. De Novo Gene Disruptions in Children on the Autistic Spectrum. Neuron 2012; 74: 285-299.
43. Rauch A, Wieczorek D, Graf E, Wieland T, Endele S, Schwarzmayr T et al. Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study. Lancet 2012; 380: 1674-1682.
44. De Ligt J, Willemsen MH, van Bon BW, Kleefstra T, Yntema HG, Kroes T et al. Diagnostic exome sequencing in persons with severe intellectual disability. N Engl J Med 2012; 367: 1921-1929.
45. Kong A, Frigge ML, Masson G, Besenbacher S, Sulem P, Magnusson G et al. Rate of de novo mutations and the importance of fathers age to disease risk. Nature 2012; 488: 471-475.
46. McGrath JJ, Petersen L, Agerbo E, Mors O, Mortensen PB, Pedersen CB et al. A comprehensive assessment of parental age and psychiatric disorders. JAMA Psychiatry 2014; 71: 301-309.
47. McCarthy SE, Gillis J, Kramer M, Lihm J, Yoon S, Berstein Y et al. De novo mutations in schizophrenia implicate chromatin remodeling and support a genetic overlap with autism and intellectual disability. Mol Psychiatry 2014; 19: 652-658.
48. Craddock N, Owen MJ. The Kraepelinian dichotomy-going, going... but still not gone. Br J Psychiatry 2010; 196: 92-95.
49. Doherty JL, Owen MJ. The Research Domain Criteria: moving the goalposts to change the game. Br J Psychiatry 2014; 204: 171-173.
50. Doherty JL, Owen MJ. Genomic insights into the overlap between psychiatric disorders: implications for research and clinical practice. Genome Med 2014; 6: 29.
51. McCarroll SA, Hyman SE. Progress in the genetics of polygenic brain disorders: significant new challenges for neurobiology. Neuron 2013; 80: 578-587.
52. Gaj T, Gersbach CA, Barbas CF. ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol 2013; 31: 397-405.
53. Zhang F, Wen Y, Guo X. CRISPR/Cas9 for genome editing: progress, implications and challenges. Hum Mol Genet 2014; 23: R40-R46.
54. Linden DEJ. The challenges and promise of neuroimaging in psychiatry. Neuron 2012; 73: 8-22.