Schizophrenia genetics: Progress, at last

Current Opinion in Genetics and Development

Volumn 22, Issue 3, 2012, Pages 238-244

  Mulle, Jennifer Gladys ^a,b  

^a EMORY UNIVERSITY   (United States)

^b EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CONTACTIN ASSOCIATED PROTEIN LIKE 2; DISRUPTED IN SCHIZOPHRENIA 1 PROTEIN; GLYCOPROTEIN; NEUREXIN; NEUREXIN 1; UNCLASSIFIED DRUG; VASOACTIVE INTESTINAL POLYPEPTIDE RECEPTOR 2;

C10ORF26 GENE; CACNA1C GENE; CHROMOSOME DELETION; CHROMOSOME DELETION 15Q13; CHROMOSOME DELETION 17Q12; CHROMOSOME DELETION 1Q21; CHROMOSOME DELETION 22Q11; CHROMOSOME TRANSLOCATION; CNTNAP2 GENE; COPY NUMBER VARIATION; CSMD1 GENE; DGCR2 GENE; DISC1 GENE; EFFECT SIZE; FAMILY HISTORY; GENE; GENE FREQUENCY; GENE LOCUS; GENETIC ASSOCIATION; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; HERITABILITY; HUMAN; MEDICAL RESEARCH; NRXN1 GENE; PRIORITY JOURNAL; REVIEW; RISK ASSESSMENT; SCHIZOPHRENIA; SINGLE NUCLEOTIDE POLYMORPHISM; TCF4 GENE; VIPR2 GENE;

ALLELES; CHROMOSOME DELETION; CHROMOSOMES, HUMAN, PAIR 22; DISEASE SUSCEPTIBILITY; DNA COPY NUMBER VARIATIONS; GENE FREQUENCY; GENETIC LOCI; GENETIC PREDISPOSITION TO DISEASE; GENOME, HUMAN; GENOME-WIDE ASSOCIATION STUDY; HUMANS; INHERITANCE PATTERNS; RISK FACTORS; SCHIZOPHRENIA; TRANSLOCATION, GENETIC;

EID: 84862498540     PISSN: 0959437X     EISSN: 18790380     Source Type: Journal    
DOI: 10.1016/j.gde.2012.02.011     Document Type: Review

References (72)

1. Gottesman IIS J. Schizophrenia: The Epigenetic Puzzle 1984, Cambridge University Press, Cambridge.
2. Aleman A., Kahn R.S., Selten J.P. Sex differences in the risk of schizophrenia: evidence from meta-analysis. Arch Gen Psychiatry 2003, 60:565-571.
3. Pulver A.E., Liang K.Y., Brown C.H., Wolyniec P., McGrath J., Adler L., Tam D., Carpenter W.T., Childs B. Risk factors in schizophrenia. Season of birth, gender, and familial risk. Br J Psychiatry 1992, 160:65-71.
4. Torrey E.F., Torrey B.B., Peterson M.R. Seasonality of schizophrenic births in the United States. Arch Gen Psychiatry 1977, 34:1065-1070.
5. Davies G., Welham J., Chant D., Torrey E.F., McGrath J. A systematic review and meta-analysis of Northern Hemisphere season of birth studies in schizophrenia. Schizophr Bull 2003, 29:587-593.
6. Kendell R.E., Adams W. Unexplained fluctuations in the risk for schizophrenia by month and year of birth. Br J Psychiatry 1991, 158:758-763.
7. van Os J., Kapur S. Schizophrenia. Lancet 2009, 374:635-645.
8. Jablensky A.V., Morgan V., Zubrick S.R., Bower C., Yellachich L.A. Pregnancy, delivery, and neonatal complications in a population cohort of women with schizophrenia and major affective disorders. Am J Psychiatry 2005, 162:79-91.
9. Preti A., Cardascia L., Zen T., Marchetti M., Favaretto G., Miotto P. Risk for obstetric complications and schizophrenia. Psychiatry Res 2000, 96:127-139.
10. Dalman C., Allebeck P. Paternal age and schizophrenia: further support for an association. Am J Psychiatry 2002, 159:1591-1592.
11. Malaspina D., Corcoran C., Fahim C., Berman A., Harkavy-Friedman J., Yale S., Goetz D., Goetz R., Harlap S., Gorman J. Paternal age and sporadic schizophrenia: evidence for de novo mutations. Am J Med Genet 2002, 114:299-303.
12. Malaspina D., Harlap S., Fennig S., Heiman D., Nahon D., Feldman D., Susser E.S. Advancing paternal age and the risk of schizophrenia. Arch Gen Psychiatry 2001, 58:361-367.
13. McGrath J.J., Susser E.S. New directions in the epidemiology of schizophrenia. Med J Aust 2009, 190:S7-S9.
14. Arias I., Sorlozano A., Villegas E., Luna J.D., McKenney K., Cervilla J., Gutierrez B., Gutierrez J. Infectious agents associated with schizophrenia: a meta-analysis. Schizophr Res 2012, 136:128-136.
15. Kety S.S., Rosenthal D., Wender P.H., Schulsinger F., Jacobsen B. Mental illness in the biological and adoptive families of adopted individuals who have become schizophrenic. Behav Genet 1976, 6:219-225.
16. Kety S.S., Rosenthal D., Wender P.H., Schulsinger F. Mental illness in the biological and adoptive families of adpoted schizophrenics. Am J Psychiatry 1971, 128:302-306.
17. Heston L.L. Psychiatric disorders in foster home reared children of schizophrenic mothers. Br J Psychiatry 1966, 112:819-825.
18. Wender P.H., Rosenthal D., Kety S.S., Schulsinger F., Welner J. Crossfostering. A research strategy for clarifying the role of genetic and experiential factors in the etiology of schizophrenia. Arch Gen Psychiatry 1974, 30:121-128.
19. Farmer A.E., McGuffin P., Gottesman I.I. Twin concordance for DSM-III schizophrenia. Scrutinizing the validity of the definition. Arch Gen Psychiatry 1987, 44:634-641.
20. Rao D.C., Morton N.E., Gottesman I.I., Lew R. Path analysis of qualitative data on pairs of relatives: application to schizophrenia. Hum Hered 1981, 31:325-333.
21. Tsuang M.T., Bucher K.D., Fleming J.A. Testing the monogenic theory of schizophrenia: an application of segregation analysis to blind family study data. Br J Psychiatry 1982, 140:595-599.
22. Risch N., Baron M. Segregation analysis of schizophrenia and related disorders. Am J Hum Genet 1984, 36:1039-1059.
23. Sullivan P.F., Lin D., Tzeng J.Y., van den Oord E., Perkins D., Stroup T.S., Wagner M., Lee S., Wright F.A., Zou F., et al. Genomewide association for schizophrenia in the CATIE study: results of stage 1. Mol Psychiatry 2008, 13:570-584.
24. 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.
25. Need A.C., Ge D., Weale M.E., Maia J., Feng S., Heinzen E.L., Shianna K.V., Yoon W., Kasperaviciute D., Gennarelli M., et al. A genome-wide investigation of SNPs and CNVs in schizophrenia. PLoS Genet 2009, 5:e1000373.
26. 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.
27. Stefansson H., Ophoff R.A., Steinberg S., Andreassen O.A., Cichon S., Rujescu D., Werge T., Pietilainen O.P., Mors O., Mortensen P.B., et al. Common variants conferring risk of schizophrenia. Nature 2009, 460:744-747.
28. Shi J., Levinson D.F., Duan J., Sanders A.R., Zheng Y., Pe'er I., Dudbridge F., Holmans P.A., Whittemore A.S., Mowry B.J., et al. Common variants on chromosome 6p22.1 are associated with schizophrenia. Nature 2009, 460:753-757.
29. Ripke S., Sanders A.R., Kendler K.S., Levinson D.F., Sklar P., Holmans P.A., Lin D.Y., Duan J., Ophoff R.A., Andreassen O.A., et al. Genome-wide association study identifies five new schizophrenia loci. Nat Genet 2011, 43:969-976.
30. Smrt R.D., Szulwach K.E., Pfeiffer R.L., Li X., Guo W., Pathania M., Teng Z.Q., Luo Y., Peng J., Bordey A., et al. MicroRNA miR-137 regulates neuronal maturation by targeting ubiquitin ligase mind bomb-1. Stem Cells 2010, 28:1060-1070.
31. Szulwach K.E., Li X., Smrt R.D., Li Y., Luo Y., Lin L., Santistevan N.J., Li W., Zhao X., Jin P. Cross talk between microRNA and epigenetic regulation in adult neurogenesis. J Cell Biol 2010, 189:127-141.
32. Karayiorgou M., Morris M.A., Morrow B., Shprintzen R.J., Goldberg R., Borrow J., Gos A., Nestadt G., Wolyniec P.S., Lasseter V.K., et al. Schizophrenia susceptibility associated with interstitial deletions of chromosome 22q11. Proc Natl Acad Sci USA 1995, 92:7612-7616.
33. Ivanov D., Kirov G., Norton N., Williams H.J., Williams N.M., Nikolov I., Tzwetkova R., Stambolova S.M., Murphy K.C., Toncheva D., et al. Chromosome 22q11 deletions, velo-cardio-facial syndrome and early-onset psychosis. Molecular genetic study. Br J Psychiatry 2003, 183:409-413.
34. Sporn A., Addington A., Reiss A.L., Dean M., Gogtay N., Potocnik U., Greenstein D., Hallmayer J., Gochman P., Lenane M., et al. 22q11 deletion syndrome in childhood onset schizophrenia: an update. Mol Psychiatry 2004, 9:225-226.
35. Gothelf D., Presburger G., Zohar A.H., Burg M., Nahmani A., Frydman M., Shohat M., Inbar D., Aviram-Goldring A., Yeshaya J., et al. Obsessive-compulsive disorder in patients with velocardiofacial (22q11 deletion) syndrome. Am J Med Genet B Neuropsychiatr Genet 2004, 126:99-105.
36. Ryan A.K., Goodship J.A., Wilson D.I., Philip N., Levy A., Seidel H., Schuffenhauer S., Oechsler H., Belohradsky B., Prieur M., et al. Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study. J Med Genet 1997, 34:798-804.
37. Bassett A.S., Chow E.W., Husted J., Weksberg R., Caluseriu O., Webb G.D., Gatzoulis M.A. Clinical features of 78 adults with 22q11 Deletion Syndrome. Am J Med Genet A 2005, 138:307-313.
38. Liu H., Heath S.C., Sobin C., Roos J.L., Galke B.L., Blundell M.L., Lenane M., Robertson B., Wijsman E.M., Rapoport J.L., et al. Genetic variation at the 22q11 PRODH2/DGCR6 locus presents an unusual pattern and increases susceptibility to schizophrenia. Proc Natl Acad Sci USA 2002, 99:3717-3722.
39. Li T., Ma X., Sham P.C., Sun X., Hu X., Wang Q., Meng H., Deng W., Liu X., Murray R.M., et al. Evidence for association between novel polymorphisms in the PRODH gene and schizophrenia in a Chinese population. Am J Med Genet B Neuropsychiatr Genet 2004, 129:13-15.
40. Abou Jamra R., Schumacher J., Becker T., Dahdouh F., Ohlraun S., Suliman H., Schulze T.G., Tullius M., Kovalenko S., Maier W., et al. No evidence for an association between variants at the proline dehydrogenase locus and schizophrenia or bipolar affective disorder. Psychiatr Genet 2005, 15:195-198.
41. Ohtsuki T., Tanaka S., Ishiguro H., Noguchi E., Arinami T., Tanabe E., Yara K., Okubo T., Takahashi S., Matsuura M., et al. Failure to find association between PRODH deletion and schizophrenia. Schizophr Res 2004, 67:111-113.
42. Williams H.J., Williams N., Spurlock G., Norton N., Zammit S., Kirov G., Owen M.J., O'Donovan M.C. Detailed analysis of PRODH and PsPRODH reveals no association with schizophrenia. Am J Med Genet B Neuropsychiatr Genet 2003, 120:42-46.
43. Li T., Sham P.C., Vallada H., Xie T., Tang X., Murray R.M., Liu X., Collier D.A. Preferential transmission of the high activity allele of COMT in schizophrenia. Psychiatr Genet 1996, 6:131-133.
44. Shifman S., Bronstein M., Sternfeld M., Pisante-Shalom A., Lev-Lehman E., Weizman A., Reznik I., Spivak B., Grisaru N., Karp L., et al. A highly significant association between a COMT haplotype and schizophrenia. Am J Hum Genet 2002, 71:1296-1302.
45. Glatt S.J., Faraone S.V., Tsuang M.T. Association between a functional catechol O-methyltransferase gene polymorphism and schizophrenia: meta-analysis of case-control and family-based studies. Am J Psychiatry 2003, 160:469-476.
46. Williams H.J., Glaser B., Williams N.M., Norton N., Zammit S., MacGregor S., Kirov G.K., Owen M.J., O'Donovan M.C. No association between schizophrenia and polymorphisms in COMT in two large samples. Am J Psychiatry 2005, 162:1736-1738.
47. Blackwood D.H., Fordyce A., Walker M.T., St Clair D.M., Porteous D.J., Muir W.J. 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, 69:428-433.
48. Hodgkinson C.A., Goldman D., Jaeger J., Persaud S., Kane J.M., Lipsky R.H., Malhotra A.K. Disrupted in schizophrenia 1 (DISC1): association with schizophrenia, schizoaffective disorder, and bipolar disorder. Am J Hum Genet 2004, 75:862-872.
49. Sebat J., Lakshmi B., Troge J., Alexander J., Young J., Lundin P., Maner S., Massa H., Walker M., Chi M., et al. Large-scale copy number polymorphism in the human genome. Science 2004, 305:525-528.
50. Iafrate A.J., Feuk L., Rivera M.N., Listewnik M.L., Donahoe P.K., Qi Y., Scherer S.W., Lee C. Detection of large-scale variation in the human genome. Nat Genet 2004, 36:949-951.
51. Walsh T., McClellan J.M., McCarthy S.E., Addington A.M., Pierce S.B., Cooper G.M., Nord A.S., Kusenda M., Malhotra D., Bhandari A., et al. Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science 2008, 320:539-543.
52. 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.
53. Stefansson H., Rujescu D., Cichon S., Pietilainen O.P., Ingason A., Steinberg S., Fossdal R., Sigurdsson E., Sigmundsson T., Buizer-Voskamp J.E., et al. Large recurrent microdeletions associated with schizophrenia. Nature 2008, 455:232-236.
54. Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature 2008, 455:237-241. International Schizophrenia Consortium.
55. Moreno-De-Luca D., Mulle J.G., Kaminsky E.B., Sanders S.J., Myers S.M., Adam M.P., Pakula A.T., Eisenhauer N.J., Uhas K., Weik L., et al. Deletion 17q12 is a recurrent copy number variant that confers high risk of autism and schizophrenia. Am J Hum Genet 2010, 87:618-630.
56. Mulle J.G., Dodd A.F., McGrath J.A., Wolyniec P.S., Mitchell A.A., Shetty A.C., Sobreira N.L., Valle D., Rudd M.K., Satten G., et al. Microdeletions of 3q29 confer high risk for schizophrenia. Am J Hum Genet 2010, 87:229-236.
57. Levinson D.F., Duan J., Oh S., Wang K., Sanders A.R., Shi J., Zhang N., Mowry B.J., Olincy A., Amin F., et al. Copy number variants in schizophrenia: confirmation of five previous findings and new evidence for 3q29 microdeletions and VIPR2 duplications. Am J Psychiatry 2011, 168:302-316.
58. McCarthy S.E., Makarov V., Kirov G., Addington A.M., McClellan J., Yoon S., Perkins D.O., Dickel D.E., Kusenda M., Krastoshevsky O., et al. Microduplications of 16p11.2 are associated with schizophrenia. Nat Genet 2009, 41:1223-1227.
59. Kirov G., Gumus D., Chen W., Norton N., Georgieva L., Sari M., O'Donovan M.C., Erdogan F., Owen M.J., Ropers H.H., et al. Comparative genome hybridization suggests a role for NRXN1 and APBA2 in schizophrenia. Hum Mol Genet 2008, 17:458-465.
60. Rujescu D., Ingason A., Cichon S., Pietilainen O.P., Barnes M.R., Toulopoulou T., Picchioni M., Vassos E., Ettinger U., Bramon E., et al. Disruption of the neurexin 1 gene is associated with schizophrenia. Hum Mol Genet 2009, 18:988-996.
61. Kirov G., Rujescu D., Ingason A., Collier D.A., O'Donovan M.C., Owen M.J. Neurexin 1 (NRXN1) deletions in schizophrenia. Schizophr Bull 2009, 35:851-854.
62. Friedman J.I., Vrijenhoek T., Markx S., Janssen I.M., van der Vliet W.A., Faas B.H., Knoers N.V., Cahn W., Kahn R.S., Edelmann L., et al. CNTNAP2 gene dosage variation is associated with schizophrenia and epilepsy. Mol Psychiatry 2008, 13:261-266.
63. Vacic V., McCarthy S., Malhotra D., Murray F., Chou H.H., Peoples A., Makarov V., Yoon S., Bhandari A., Corominas R., et al. Duplications of the neuropeptide receptor gene VIPR2 confer significant risk for schizophrenia. Nature 2011, 471:499-503.
64. Cubells J.F., Deoreo E.H., Harvey P.D., Garlow S.J., Garber K., Adam M.P., Martin C.L. Pharmaco-genetically guided treatment of recurrent rage outbursts in an adult male with 15q13.3 deletion syndrome. Am J Med Genet A 2011, 155A:805-810.
65. Akil H., Brenner S., Kandel E., Kendler K.S., King M.C., Scolnick E., Watson J.D., Zoghbi H.Y. Medicine. The future of psychiatric research: genomes and neural circuits. Science 2010, 327:1580-1581.
66. Mefford H.C., Sharp A.J., Baker C., Itsara A., Jiang Z., Buysse K., Huang S., Maloney V.K., Crolla J.A., Baralle D., et al. Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes. N Engl J Med 2008, 359:1685-1699.
67. Szatmari P., Paterson A.D., Zwaigenbaum L., Roberts W., Brian J., Liu X.Q., Vincent J.B., Skaug J.L., Thompson A.P., Senman L., et al. Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nat Genet 2007, 39:319-328.
68. Mefford H.C., Clauin S., Sharp A.J., Moller R.S., Ullmann R., Kapur R., Pinkel D., Cooper G.M., Ventura M., Ropers H.H., et al. Recurrent reciprocal genomic rearrangements of 17q12 are associated with renal disease, diabetes, and epilepsy. Am J Hum Genet 2007, 81:1057-1069.
69. Sharp A.J., Mefford H.C., Li K., Baker C., Skinner C., Stevenson R.E., Schroer R.J., Novara F., De Gregori M., Ciccone R., et al. A recurrent 15q13.3 microdeletion syndrome associated with mental retardation and seizures. Nat Genet 2008, 40:322-328.
70. 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.
71. Xu B., Roos J.L., Dexheimer P., Boone B., Plummer B., Levy S., Gogos J.A., Karayiorgou M. Exome sequencing supports a de novo mutational paradigm for schizophrenia. Nat Genet 2011, 43:864-868.
72. Girard S.L., Gauthier J., Noreau A., Xiong L., Zhou S., Jouan L., Dionne-Laporte A., Spiegelman D., Henrion E., Diallo O., et al. Increased exonic de novo mutation rate in individuals with schizophrenia. Nat Genet 2011, 43:860-863.