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What have the genomics ever done for the psychoses?

Published online by Cambridge University Press:  12 October 2009

M. Gill ,
G. Donohoe  and
A. Corvin
M. Gill*
Affiliation:
Neuropsychiatric Genetics Research Group, Department of Psychiatry, School of Medicine, Trinity College Dublin, Ireland
G. Donohoe
Affiliation:
Neuropsychiatric Genetics Research Group, Department of Psychiatry, School of Medicine, Trinity College Dublin, Ireland
A. Corvin
Affiliation:
Neuropsychiatric Genetics Research Group, Department of Psychiatry, School of Medicine, Trinity College Dublin, Ireland
*
*Address for correspondence: Professor M. Gill, Department of Psychiatry, Trinity Center for Health Sciences, St. James' Hospital, Dublin 8, Ireland. (Email: [email protected])
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Abstract

Background

Despite the substantial heritability of the psychoses and their genuine public health burden, the applicability of the genomic approach in psychiatry has been strongly questioned or prematurely dismissed.

Method

A selective review of the recent literature on molecular genetic and genomic approaches to the psychoses including the early output from genome-wide association studies and the genomic analysis of DNA structural variation.

Results

Susceptibility variants at strong candidate genes have been identified including neuregulin, dysbindin, DISC1 and neurexin 1. Rare but highly penetrant copy number variants and new mutations affecting genes involved in neurodevelopment, cell signalling and synaptic function have been described showing some overlapping genetic architecture with other developmental disorders including autism. The de-novo mutations described offer an explanation for the familial sporadic divide and the persistence of schizophrenia in the population. The functional effects of risk variants at the level of cognition and connectivity has been described and recently, ZNF804A has been identified, and the MHC re-identified as risk loci, and it has been shown that at least a third of the variation in liability is due to multiple common risk variants of small effect with a substantial shared genetic liability between schizophrenia and bipolar affective disorder.

Conclusions

The genomics have done much for the psychoses to date and more is anticipated.

Keywords

Copy number variationDNA variantsgeneticspsychosisschizophrenia
Type
Review Article
Information
Psychological Medicine , Volume 40 , Issue 4 , April 2010 , pp. 529 - 540
Copyright
Copyright © Cambridge University Press 2009

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References

Aggarwal, VS, Morrow, BE (2008). Genetic modifiers of the physical malformations in velo-cardio-facial syndrome/DiGeorge syndrome. Developmental Disability Research Reviews 14, 19–25.CrossRefGoogle ScholarPubMed
Arinami, T (2006). Analyses of the associations between the genes of 22q11 deletion syndrome and schizophrenia. Journal of Human Genetics 51, 1037–1045.CrossRefGoogle ScholarPubMed
Austin, CP, Ky, B, Ma, L, Morris, JA, Shughrue, PJ (2004). Expression of Disrupted-In-Schizophrenia-1, a schizophrenia-associated gene, is prominent in the mouse hippocampus throughout brain development. Neuroscience 124, 3–10.CrossRefGoogle ScholarPubMed
Blackwood, DH, Fordyce, A, Walker, MT, St Clair, DM, Porteous, DJ, Muir, WJ (2001). Schizophrenia and affective disorders – cosegregation with a translocation at chromosome 1q42 that directly disrupts brain-expressed genes: clinical and P300 findings in a family. American Journal of Human Genetics 69, 428–433.CrossRefGoogle ScholarPubMed
Bray, NJ, Preece, A, Williams, NM, Moskvina, V, Buckland, PR, Owen, MJ, O'Donovan, MC (2005). Haplotypes at the dystrobrevin binding protein 1 (DTNBP1) gene locus mediate risk for schizophrenia through reduced DTNBP1 expression. Human Molecular Genetics 14, 1947–1954.CrossRefGoogle ScholarPubMed
Burdick, KE, Goldberg, TE, Funke, B, Bates, JA, Lencz, T, Kucherlapati, R, Malhotra, AK (2007). DTNBP1 genotype influences cognitive decline in schizophrenia. Schizophrenia Research 89, 169–172.CrossRefGoogle ScholarPubMed
Burdick, KE, Hodgkinson, CA, Szeszko, PR, Lencz, T, Ekholm, JM, Kane, JM, Goldman, D, Malhotra, AK (2005). DISC1 and neurocognitive function in schizophrenia. Neuroreport 16, 1399–1402.CrossRefGoogle ScholarPubMed
Burdick, KE, Lencz, T, Funke, B, Finn, CT, Szeszko, PR, Kane, JM, Kucherlapati, R, Malhotra, AK (2006). Genetic variation in DTNBP1 influences general cognitive ability. Human Molecular Genetics 15, 1563–1568.CrossRefGoogle ScholarPubMed
Camargo, LM, Collura, V, Rain, JC, Mizuguchi, K, Hermjakob, H, Kerrien, S, Bonnert, TP, Whiting, PJ, Brandon, NJ (2007). Disrupted in Schizophrenia 1 interactome: evidence for the close connectivity of risk genes and a potential synaptic basis for schizophrenia. Molecular Psychiatry 12, 74–86.CrossRefGoogle Scholar
Cannon, TD, Hennah, W, van Erp, TG, Thompson, PM, Lonnqvist, J, Huttunen, M, Gasperoni, T, Tuulio-Henriksson, A, Pirkola, T, Toga, AW, Kaprio, J, Mazziotta, J, Peltonen, L (2005). Association of DISC1/TRAX haplotypes with schizophrenia, reduced prefrontal gray matter, and impaired short- and long-term memory. Archives of General Psychiatry 62, 1205–1213.CrossRefGoogle ScholarPubMed
Cedazo-Mínguez, A (2007). Apolipoprotein E and Alzheimer's disease: molecular mechanisms and therapeutic opportunities. Journal Cellular and Molecular Medicine 11, 1227–1238.CrossRefGoogle ScholarPubMed
Chubb, JE, Bradshaw, NJ, Soares, DC, Porteous, DJ, Millar, JK (2008). The DISC locus in psychiatric illness. Molecular Psychiatry 13, 36–64.CrossRefGoogle ScholarPubMed
Corvin, A, Donohoe, G, Nangle, JM, Schwaiger, S, Morris, D, Gill, M (2008). A dysbindin risk haplotype associated with less severe manic-type symptoms in psychosis. Neuroscience Letters 431, 146–149.CrossRefGoogle ScholarPubMed
Corvin, AP, Morris, DW, McGhee, K, Schwaiger, S, Scully, P, Quinn, J, Meagher, D, Clair, DS, Waddington, JL, Gill, M (2004). Confirmation and refinement of an ‘at-risk’ haplotype for schizophrenia suggests the EST cluster, Hs.97362, as a potential susceptibility gene at the Neuregulin-1 locus. Molecular Psychiatry 9, 208–213.CrossRefGoogle ScholarPubMed
Craddock, N, O'Donovan, MC, Owen, MJ (2006). Genes for schizophrenia and bipolar disorder? Implications for psychiatric nosology. Schizophrenia Bulletin 32, 9–16.CrossRefGoogle ScholarPubMed
Craig, AM, Kang, Y (2007). Neurexin-neuroligin signaling in synapse development. Current Opinions in Neurobiology 17, 43–52.CrossRefGoogle ScholarPubMed
Crow, TJ (2008). The emperors of the schizophrenia polygene have no clothes. Psychological Medicine 38, 1681–1685.CrossRefGoogle ScholarPubMed
Demirhan, O, Taştemir, D (2003). Chromosome aberrations in a schizophrenia population. Schizophrenia Research 65, 1–7.CrossRefGoogle Scholar
Donohoe, G, Morris, DW, Clarke, S, McGhee, KA, Schwaiger, S, Nangle, JM, Garavan, H, Robertson, IH, Gill, M, Corvin, A (2007). Variance in neurocognitive performance is associated with dysbindin-1 in schizophrenia: a preliminary study. Neuropsychologia 45, 454–458.CrossRefGoogle ScholarPubMed
Donohoe, G, Morris, DW, De Sanctis, P, Magno, E, Montesi, JL, Garavan, HP, Robertson, IH, Javitt, DC, Gill, M, Corvin, AP, Foxe, JJ (2008). Early visual processing deficits in dysbindin-associated schizophrenia. Biological Psychiatry 63, 484–489.CrossRefGoogle ScholarPubMed
Duan, X, Chang, JH, Ge, S, Faulkner, RL, Kim, JY, Kitabatake, Y, Liu, XB, Yang, CH, Jordan, JD, Ma, DK, Liu, CY, Ganesan, S, Cheng, HJ, Ming, GL, Lu, B, Song, H (2007). Disrupted-In-Schizophrenia 1 regulates integration of newly generated neurons in the adult brain. Cell 130, 1146–1158.CrossRefGoogle ScholarPubMed
Dubois, PC, van Heel, DA (2008). New susceptibility genes for ulcerative colitis. Nature Genetics 40, 686–688.CrossRefGoogle ScholarPubMed
Egeland, JA, Gerhard, DS, Pauls, DL, Sussex, JN, Kidd, KK, Allen, CR, Hostetter, AM, Housman, DE (1987). Bipolar affective disorders linked to DNA markers on chromosome 11. Nature 325, 783–787.CrossRefGoogle ScholarPubMed
Esslinger, C, Walter, H, Kirsch, P, Erk, S, Schnell, K, Arnold, C, Haddad, L, Mier, D, Optiz von Boberfeld, C, Raab, K, Witt, SH, Rietschel, M, Cichon, S, Meyer-Lindenberg, A (2009). Neural mechanisms of a genome-wide supported psychosis variant. Science 324, 605.CrossRefGoogle ScholarPubMed
Fallgatter, AJ, Herrmann, MJ, Hohoff, C, Ehlis, AC, Jarczok, TA, Freitag, CM, Deckert, J (2006). DTNBP1 (dysbindin) gene variants modulate prefrontal brain function in healthy individuals. Neuropsychopharmacology 31, 2002–2010.CrossRefGoogle ScholarPubMed
Fanous, AH, van den Oord, EJ, Riley, BP, Aggen, SH, Neale, MC, O'Neill, FA, Walsh, D, Kendler, KS (2005). Relationship between a high-risk haplotype in the DTNBP1 (dysbindin) gene and clinical features of schizophrenia. American Journal of Psychiatry 162, 1824–1832.CrossRefGoogle ScholarPubMed
Ferreira, MA, O'Donovan, MC, Meng, YA, Jones, IR, Ruderfer, DM, Jones, L, Fan, J, Kirov, G, Perlis, RH, Green, EK, Smoller, JW, Grozeva, D, Stone, J, Nikolov, I, Chambert, K, Hamshere, ML, Nimgaonkar, VL, Moskvina, V, Thase, ME, Caesar, S, Sachs, GS, Franklin, J, Gordon-Smith, K, Ardlie, KG, Gabriel, SB, Fraser, C, Blumenstiel, B, Defelice, M, Breen, G, Gill, M, Morris, DW, Elkin, A, Muir, WJ, McGhee, KA, Williamson, R, MacIntyre, DJ, MacLean, AW, St, CD, Robinson, M, Van Beck, M, Pereira, AC, Kandaswamy, R, McQuillin, A, Collier, DA, Bass, NJ, Young, AH, Lawrence, J, Ferrier, IN, Anjorin, A, Farmer, A, Curtis, D, Scolnick, EM, McGuffin, P, Daly, MJ, Corvin, AP, Holmans, PA, Blackwood, DH, Gurling, HM, Owen, MJ, Purcell, SM, Sklar, P, Craddock, N, Wellcome Trust Case Control Consortium (2008). Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Nature Genetics 40, 1056–1058.CrossRefGoogle ScholarPubMed
Friedman, JI, Vrijenhoek, T, Markx, S, Janssen, IM, van der Vliet, WA, Faas, BH, Knoers, NV, Cahn, W, Kahn, RS, Edelmann, L, Davis, KL, Silverman, JM, Brunner, HG, van Kessel, AG, Wijmenga, C, Ophoff, RA, Veltman, JA (2008). CNTNAP2 gene dosage variation is associated with schizophrenia and epilepsy. Molecular Psychiatry 13, 261–266.CrossRefGoogle Scholar
Gothelf, D, Schaer, M, Eliez, S (2008). Genes, brain development and psychiatric phenotypes in velo-cardio-facial syndrome. Developmental Disabilities Research Reviews 14, 59–68.CrossRefGoogle ScholarPubMed
Hahn, CG, Wang, HY, Cho, DS, Talbot, K, Gur, RE, Berrettini, WH, Bakshi, K, Kamins, J, Borgmann-Winter, KE, Siegel, SJ, Gallop, RJ, Arnold, SE (2006). Altered neuregulin 1-erbB4 signaling contributes to NMDA receptor hypofunction in schizophrenia. Nature Medicine 12, 824–828.CrossRefGoogle ScholarPubMed
Harrison, PJ, Law, AJ (2006). Neuregulin 1 and schizophrenia: genetics, gene expression, and neurobiology. Biological Psychiatry 60, 132–140.CrossRefGoogle ScholarPubMed
Hennah, W, Varilo, T, Kestilä, M, Paunio, T, Arajärvi, R, Haukka, J, Parker, A, Martin, R, Levitzky, S, Partonen, T, Meyer, J, Lönnqvist, J, Peltonen, L, Ekelund, J (2003). Haplotype transmission analysis provides evidence of association for DISC1 to schizophrenia and suggests sex-dependent effects. Human Molecular Genetics 12, 3151–3159.CrossRefGoogle ScholarPubMed
Hindorff, LA, Junkins, HA, Mehta, JP, Manolio, TA (2009). A catalog of published genome-wide association studies (www.genome.gov/26525384). Accessed 23 July 2009.Google Scholar
Hindorff, LA, Sethupathy, P, Junkins, HA, Ramos, EM, Mehta, JP, Collins, FS, Manolio, TA (2009). Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proceedings of the National Academy of Sciences USA 106, 9362–9367.CrossRefGoogle ScholarPubMed
Iizuka, Y, Sei, Y, Weinberger, DR, Straub, RE (2007). Evidence that the BLOC-1 protein dysbindin modulates dopamine D2 receptor internalization and signaling but not D1 internalization. Journal of Neurosciences 27, 12390–12395.CrossRefGoogle Scholar
International Schizophrenia Consortium (2008). Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature 455, 237–241.CrossRefGoogle Scholar
International Schizophrenia Consortium (2009). Common polygenic variation contributes to risk of schizophrenia that overlaps with bipolar disorder. Nature 460, 748–752.CrossRefGoogle Scholar
Jacobs, PA, Brunton, M, Frackiewicz, A, Newton, M, Cook, PJL, Robson, EB (1970). Studies on a family with three cytogenetic markers. Annals of Human Genetics 33, 325–336.CrossRefGoogle Scholar
Karayiorgou, M, Gogos, JA (2004). The molecular genetics of the 22q11-associated schizophrenia. Brain Research. Molecular Brain Research 132, 95–104.CrossRefGoogle ScholarPubMed
Kelsoe, JR, Ginns, EI, Egeland, JA, Gerhard, DS, Goldstein, AM, Bale, SJ, Pauls, DL, Long, RT, Kidd, KK, Conte, G, Housman, DE, Paul, DM (1989). Re-evaluation of the linkage relationship between chromosome 11p loci and the gene for bipolar affective disorder in the Old Order Amish. Nature 342, 238–243.CrossRefGoogle ScholarPubMed
Kilpinen, H, Ylisaukko-Oja, T, Hennah, W, Palo, OM, Varilo, T, Vanhala, R, Nieminen-von Wendt, T, von Wendt, L, Paunio, T, Peltonen, L (2008). Association of DISC1 with autism and Asperger syndrome. Molecular Psychiatry 13, 187–196.CrossRefGoogle ScholarPubMed
Kim, HG, Kishikawa, S, Higgins, AW, Seong, IS, Donovan, DJ, Shen, Y, Lally, E, Weiss, LA, Najm, J, Kutsche, K, Descartes, M, Holt, L, Braddock, S, Troxell, R, Kaplan, L, Volkmar, F, Klin, A, Tsatsanis, K, Harris, DJ, Noens, I, Pauls, DL, Daly, MJ, MacDonald, ME, Morton, CC, Quade, BJ, Gusella, JF (2008). Disruption of neurexin 1 associated with autism spectrum disorder. American Journal of Human Genetics 82, 199–207.CrossRefGoogle ScholarPubMed
Kirov, G, Gumus, D, Chen, W, Norton, N, Georgieva, L, Sari, M, O'Donovan, MC, Erdogan, F, Owen, MJ, Ropers, HH, Ullmann, R (2008). Comparative genome hybridization suggests a role for NRXN1 and APBA2 in schizophrenia. Human Molecular Genetics 17, 458–465.CrossRefGoogle ScholarPubMed
Korbel, JO, Kim, PM, Chen, X, Urban, AE, Weissman, S, Snyder, M, Gerstein, MB (2008). The current excitement about copy-number variation: how it relates to gene duplications and protein families. Current Opinions in Structural Biology 18, 366–374.CrossRefGoogle ScholarPubMed
Liao, J, Kochilas, L, Nowotschin, S, Arnold, JS, Aggarwal, VS, Epstein, JA, Brown, MC, Adams, J, Morrow, BE (2004). Full spectrum of malformations in velo-cardio-facial syndrome/DiGeorge syndrome mouse models by altering Tbx1 dosage. Human Molecular Genetics 13, 1577–85.CrossRefGoogle ScholarPubMed
Lichtenstein, P, Yip, BH, Björk, C, Pawitan, Y, Cannon, TD, Sullivan, PF, Hultman, CM (2009). Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet 373, 234–239.CrossRefGoogle ScholarPubMed
López-Bendito, G, Cautinat, A, Sánchez, JA, Bielle, F, Flames, N, Garratt, AN, Talmage, DA, Role, LW, Charnay, P, Marín, O, Garel, S (2006). Tangential neuronal migration controls axon guidance: a role for neuregulin-1 in thalamocortical axon navigation. Cell 125, 127–142.CrossRefGoogle ScholarPubMed
McIntosh, AM, Moorhead, TW, Job, D, Lymer, GK, Muñoz Maniega, S, McKirdy, J, Sussmann, JE, Baig, BJ, Bastin, ME, Porteous, D, Evans, KL, Johnstone, EC, Lawrie, SM, Hall, J (2008). The effects of a neuregulin 1 variant on white matter density and integrity. Molecular Psychiatry 13, 1054–1059.CrossRefGoogle ScholarPubMed
MacIntyre, DJ, Blackwood, DH, Porteous, DJ, Pickard, BS, Muir, WJ (2003). Chromosomal abnormalities and mental illness. Molecular Psychiatry 8, 275–287.CrossRefGoogle ScholarPubMed
Mao, Y, Ge, X, Frank, CL, Madison, JM, Koehler, AN, Doud, MK, Tassa, C, Berry, EM, Soda, T, Singh, KK, Biechele, T, Petryshen, TL, Moon, RT, Haggarty, SJ, Tsai, LH (2009). Disrupted in schizophrenia 1 regulates neuronal progenitor proliferation via modulation of GSK3beta/beta-catenin signaling. Cell 136, 1017–1031.CrossRefGoogle ScholarPubMed
Merikangas, KR, Risch, N (2003). Will the genomics revolution revolutionize psychiatry? American Journal of Psychiatry 160, 625–635.CrossRefGoogle ScholarPubMed
Moon, HJ, Yim, SV, Lee, WK, Jeon, YW, Kim, YH, Ko, YJ, Lee, KS, Lee, KH, Han, SI, Rha, HK (2006). Identification of DNA copy-number aberrations by array-comparative genomic hybridization in patients with schizophrenia. Biochemical and Biophysical Research Communications 344, 531–539.CrossRefGoogle ScholarPubMed
O'Donovan, MC, Craddock, N, Norton, N, Williams, H, Peirce, T, Moskvina, V, Nikolov, I, Hamshere, M, Carroll, L, Georgieva, L, Dwyer, S, Holmans, P, Marchini, JL, Spencer, CC, Howie, B, Leung, HT, Hartmann, AM, Möller, HJ, Morris, DW, Shi, Y, Feng, G, Hoffmann, P, Propping, P, Vasilescu, C, Maier, W, Rietschel, M, Zammit, S, Schumacher, J, Quinn, EM, Schulze, TG, Williams, NM, Giegling, I, Iwata, N, Ikeda, M, Darvasi, A, Shifman, S, He, L, Duan, J, Sanders, AR, Levinson, DF, Gejman, PV, Cichon, S, Nöthen, MM, Gill, M, Corvin, A, Rujescu, D, Kirov, G, Owen, MJ, Buccola, NG, Mowry, BJ, Freedman, R, Amin, F, Black, DW, Silverman, JM, Byerley, WF, Cloninger, CR (2008). Molecular Genetics of Schizophrenia Collaboration. Identification of loci associated with schizophrenia by genome-wide association and follow-up. Nature Genetics 40, 1053–1055.CrossRefGoogle ScholarPubMed
Owen, MJ (1992). Will schizophrenia become a graveyard for molecular geneticists? Psychological Medicine 22, 289–293.CrossRefGoogle ScholarPubMed
Paylor, R, Glaser, B, Mupo, A, Ataliotis, P, Spencer, C, Sobotka, A, Sparks, C, Choi, CH, Oghalai, J, Curran, S, Murphy, KC, Monks, S, Williams, N, O'Donovan, MC, Owen, MJ, Scambler, PJ, Lindsay, E (2006). Tbx1 haploinsufficiency is linked to behavioral disorders in mice and humans: implications for 22q11 deletion syndrome. Proceedings of the National Academy of Sciences USA 103, 7729–7734.CrossRefGoogle ScholarPubMed
Paylor, R, Lindsay, E (2006). Mouse models of 22q11 deletion syndrome. Biological Psychiatry 59, 1172–9.CrossRefGoogle ScholarPubMed
Penrose, LS (1971). Psychiatric genetics. Psychological Medicine 1, 265–266.CrossRefGoogle ScholarPubMed
Pharoah, PD, Antoniou, AC, Easton, DF, Ponder, BAJ (2008). Polygenes, risk prediction and targeted prevention of breast cancer. New England Journal of Medicine 358, 2796–2803.CrossRefGoogle ScholarPubMed
Porteous, DJ, Millar, JK (2006). Disrupted in schizophrenia 1: building brains and memories. Trends in Molecular Medicine 12, 255–261.CrossRefGoogle ScholarPubMed
Psychiatric GWAS Consortium Steering Committee (2009). A framework for interpreting genome-wide association studies of psychiatric disorders. Molecular Psychiatry 14, 10–17.CrossRefGoogle Scholar
Rogowski, WH, Grosse, SD, Khoury, MJ (2009). Challenges of translating genetic tests into clinical and public health practice. Nature Reviews Genetics 10, 489–495.CrossRefGoogle ScholarPubMed
Rose, S (1998). What is wrong with reductionist explanations of behaviour? Novartis Foundation Symposia 213, 176–186.Google ScholarPubMed
Rujescu, D, Ingason, A, Cichon, S, Pietiläinen, OP, Barnes, MR, Toulopoulou, T, Picchioni, M, Vassos, E, Ettinger, U, Bramon, E, Murray, R, Ruggeri, M, Tosato, S, Bonetto, C, Steinberg, S, Sigurdsson, E, Sigmundsson, T, Petursson, H, Gylfason, A, Olason, PI, Hardarsson, G, Jonsdottir, GA, Gustafsson, O, Fossdal, R, Giegling, I, Möller, HJ, Hartmann, AM, Hoffmann, P, Crombie, C, Fraser, G, Walker, N, Lonnqvist, J, Suvisaari, J, Tuulio-Henriksson, A, Djurovic, S, Melle, I, Andreassen, OA, Hansen, T, Werge, T, Kiemeney, LA, Franke, B, Veltman, J, Buizer-Voskamp, JE; GROUP Investigators, Sabatti, C, Ophoff, RA, Rietschel, M, Nöthen, MM, Stefansson, K, Peltonen, L, St Clair, D, Stefansson, H, Collier, DA (2009). Disruption of the neurexin 1 gene is associated with schizophrenia. Human Molecular Genetics 18, 988–996.CrossRefGoogle ScholarPubMed
Sawamura, N, Sawa, A (2006). Disrupted-in-schizophrenia-1 (DISC1): a key susceptibility factor for major mental illnesses. Annals of the New York Academy of Sciences 1086, 126–133.CrossRefGoogle ScholarPubMed
Schurov, IL, Handford, EJ, Brandon, NJ, Whiting, PJ (2004). Expression of disrupted in schizophrenia 1 (DISC1) protein in the adult and developing mouse brain indicates its role in neurodevelopment. Molecular Psychiatry 9, 1100–1110.CrossRefGoogle ScholarPubMed
Schwartz, JI, Dunbar, S, Yuan, J, Li, S, Gipson, A, Rosko, K, Johnson-Levonas, AO, Lasseter, KC, Addy, C, Stoch, AS, Wagner, JA (2008). Influence of taranabant, a cannabinoid-1 receptor inverse agonist, on pharmacokinetics and pharmacodynamics of warfarin. Advanced Therapeutics 25, 1175–1190.Google ScholarPubMed
Sebat, J (2007). Major changes in our DNA lead to major changes in our thinking. Nature Genetics 39 (7 Suppl.), S3–5.CrossRefGoogle ScholarPubMed
Sebat, J, Lakshmi, B, Troge, J, Alexander, J, Young, J, Lundin, P, Månér, S, Massa, H, Walker, M, Chi, M, Navin, N, Lucito, R, Healy, J, Hicks, J, Ye, K, Reiner, A, Gilliam, TC, Trask, B, Patterson, N, Zetterberg, A, Wigler, M (2004). Large-scale copy number polymorphism in the human genome. Science 305, 525–528.CrossRefGoogle ScholarPubMed
Sherrington, R, Brynjolfsson, J, Petursson, H, Potter, M, Dudleston, K, Barraclough, B, Wasmuth, J, Dobbs, M, Gurling, H (1988). Localization of a susceptibility locus for schizophrenia on chromosome 5. Nature 336, 164–167.CrossRefGoogle ScholarPubMed
Shifman, S, Johannesson, M, Bronstein, M, Chen, SX, Collier, DA, Craddock, NJ, Kendler, KS, Li, T, O'Donovan, M, O'Neill, FA, Owen, MJ, Walsh, D, Weinberger, DR, Sun, C, Flint, J, Darvasi, A (2008). Genome-wide association identifies a common variant in the reelin gene that increases the risk of schizophrenia only in women. PLoS Genetics 4, e28.CrossRefGoogle ScholarPubMed
Stark, KL, Xu, B, Bagchi, A, Lai, WS, Liu, H, Hsu, R, Wan, X, Pavlidis, P, Mills, AA, Karayiorgou, M, Gogos, JA (2008). Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model. Nature Genetics 40, 751–760.CrossRefGoogle Scholar
St Clair, D, Blackwood, D, Muir, W, Carothers, A, Walker, M, Spowart, G, Gosden, C, Evans, HJ (1990). Association within a family of a balanced autosomal translocation with major mental illness. Lancet 336, 13–16.CrossRefGoogle ScholarPubMed
Stefanis, NC, Trikalinos, TA, Avramopoulos, D, Smyrnis, N, Evdokimidis, I, Ntzani, EE, Ioannidis, JP, Stefanis, CN (2007). Impact of schizophrenia candidate genes on schizotypy and cognitive endophenotypes at the population level. Biological Psychiatry 62, 784–792.CrossRefGoogle ScholarPubMed
Stefansson, H, Rujescu, D, Cichon, S, Pietiläinen, OP, Ingason, A, Steinberg, S, Fossdal, R, Sigurdsson, E, Sigmundsson, T, Buizer-Voskamp, JE, Hansen, T, Jakobsen, KD, Muglia, P, Francks, C, Matthews, PM, Gylfason, A, Halldorsson, BV, Gudbjartsson, D, Thorgeirsson, TE, Sigurdsson, A, Jonasdottir, A, Jonasdottir, A, Bjornsson, A, Mattiasdottir, S, Blondal, T, Haraldsson, M, Magnusdottir, BB, Giegling, I, Möller, HJ, Hartmann, A, Shianna, KV, Ge, D, Need, AC, Crombie, C, Fraser, G, Walker, N, Lonnqvist, J, Suvisaari, J, Tuulio-Henriksson, A, Paunio, T, Toulopoulou, T, Bramon, E, Di Forti, M, Murray, R, Ruggeri, M, Vassos, E, Tosato, S, Walshe, M, Li, T, Vasilescu, C, Mühleisen, TW, Wang, AG, Ullum, H, Djurovic, S, Melle, I, Olesen, J, Kiemeney, LA, Franke, B; GROUP, Sabatti, C, Freimer, NB, Gulcher, JR, Thorsteinsdottir, U, Kong, A, Andreassen, OA, Ophoff, RA, Georgi, A, Rietschel, M, Werge, T, Petursson, H, Goldstein, DB, Nöthen, MM, Peltonen, L, Collier, DA, St Clair, D, Stefansson, K (2008). Large recurrent microdeletions associated with schizophrenia. Nature 455, 232–236.CrossRefGoogle ScholarPubMed
Stefansson, H, Sigurdsson, E, Steinthorsdottir, V, Bjornsdottir, S, Sigmundsson, T, Ghosh, S, Brynjolfsson, J, Gunnarsdottir, S, Ivarsson, O, Chou, TT, Hjaltason, O, Birgisdottir, B, Jonsson, H, Gudnadottir, VG, Gudmundsdottir, E, Bjornsson, A, Ingvarsson, B, Ingason, A, Sigfusson, S, Hardardottir, H, Harvey, RP, Lai, D, Zhou, M, Brunner, D, Mutel, V, Gonzalo, A, Lemke, G, Sainz, J, Johannesson, G, Andresson, T, Gudbjartsson, D, Manolescu, A, Frigge, ML, Gurney, ME, Kong, A, Gulcher, JR, Petursson, H, Stefansson, K (2002). Neuregulin 1 and susceptibility to schizophrenia. American Journal of Human Genetics 71, 877–892.CrossRefGoogle ScholarPubMed
Südhof, TC (2008). Neuroligins and neurexins link synaptic function to cognitive disease. Nature 455, 903–911.CrossRefGoogle ScholarPubMed
Sullivan, PF, Lin, D, Tzeng, JY, van den Oord, E, Perkins, D, Stroup, TS, Wagner, M, Lee, S, Wright, FA, Zou, F, Lin, W, Downing, AM, Lieberman, J, Close, SL (2008). Genomewide association for schizophrenia in the CATIE Study: results of stage 1. Molecular Psychiatry 13, 570–584.CrossRefGoogle ScholarPubMed
Talbot, K, Eidem, WL, Tinsley, CL, Benson, MA, Thompson, EW, Smith, RJ, Hahn, CG, Siegel, SJ, Trojanowski, JQ, Gur, RE, Blake, DJ, Arnold, SE (2004). Dysbindin-1 is reduced in intrinsic, glutamatergic terminals of the hippocampal formation in schizophrenia. Journal of Clinical Investigation 113, 1353–1363.CrossRefGoogle ScholarPubMed
Urban, AE, Korbel, JO, Selzer, R, Richmond, T, Hacker, A, Popescu, GV, Cubells, JF, Green, R, Emanuel, BS, Gerstein, MB, Weissman, SM, Snyder, M (2006). High-resolution mapping of DNA copy alterations in human chromosome 22 using high-density tiling oligonucleotide arrays. Procedures of the National Academy of Sciences USA 103, 4534–4539.CrossRefGoogle ScholarPubMed
van den Oord, EJ (2002). Association studies in psychiatric genetics: what are we doing? Molecular Psychiatry 7, 827–828.CrossRefGoogle ScholarPubMed
Walsh, T, McClellan, JM, McCarthy, SE, Addington, AM, Pierce, SB, Cooper, GM, Nord, AS, Kusenda, M, Malhotra, D, Bhandari, A, Stray, SM, Rippey, CF, Roccanova, P, Makarov, V, Lakshmi, B, Findling, RL, Sikich, L, Stromberg, T, Merriman, B, Gogtay, N, Butler, P, Eckstrand, K, Noory, L, Gochman, P, Long, R, Chen, Z, Davis, S, Baker, C, Eichler, EE, Meltzer, PS, Nelson, SF, Singleton, AB, Lee, MK, Rapoport, JL, King, MC, Sebat, J (2008). Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science 320, 539–543.CrossRefGoogle ScholarPubMed
Wang, K, Zhang, H, Ma, D, Bucan, M, Glessner, JT, Abrahams, BS, Salyakina, D, Imielinski, M, Bradfield, JP, Sleiman, PM, Kim, CE, Hou, C, Frackelton, E, Chiavacci, R, Takahashi, N, Sakurai, T, Rappaport, E, Lajonchere, CM, Munson, J, Estes, A, Korvatska, O, Piven, J, Sonnenblick, LI, Alvarez Retuerto, AI, Herman, EI, Dong, H, Hutman, T, Sigman, M, Ozonoff, S, Klin, A, Owley, T, Sweeney, JA, Brune, CW, Cantor, RM, Bernier, R, Gilbert, JR, Cuccaro, ML, McMahon, WM, Miller, J, State, MW, Wassink, TH, Coon, H, Levy, SE, Schnitz, RT, Nurnberger, JI, Haines, JL, Sutcliffe, JS, Cook, EH, Minshew, NJ, Buxbaum, JD, Dawson, G, Grant, SF, Geschwind, DH, Pericak-Vance, MA, Schelienberg, GD, Hakonarson, H (2009). Common genetic variants on 5p14.1 associate with autism spectrum disorders Nature 459, 528–533.CrossRefGoogle ScholarPubMed
Weickert, CS, Straub, RE, McClintock, BW, Matsumoto, M, Hashimoto, R, Hyde, TM, Herman, MM, Weinberger, DR, Kleinman, JE (2004). Human dysbindin (DTNBP1) gene expression in normal brain and in schizophrenic prefrontal cortex and midbrain. Archives of General Psychiatry 61, 544–555.CrossRefGoogle ScholarPubMed
Williams, NM, O'Donovan, MC, Owen, MJ (2005). Is the dysbindin gene (DTNBP1) a susceptibility gene for schizophrenia? Schizophrenia Bulletin 31, 800–805.CrossRefGoogle ScholarPubMed
Wilson, GM, Flibotte, S, Chopra, V, Melnyk, BL, Honer, WG, Holt, RA (2006). DNA copy-number analysis in bipolar disorder and schizophrenia reveals aberrations in genes involved in glutamate signaling. Human Molecular Genetics 15, 743–749.CrossRefGoogle ScholarPubMed
Xu, B, Roos, JL, Levy, S, van Rensburg, EJ, Gogos, JA, Karayiorgou, M (2008). Strong association of de novo copy number mutations with sporadic schizophrenia. Nature Genetics 40, 880–885.CrossRefGoogle ScholarPubMed
Zeggini, E, Scott, LJ, Saxena, R, Voight, BF, Marchini, JL, Hu, T, de Bakker, PI, Abecasis, GR, Almgren, P, Andersen, G, Ardlie, K, Boström, KB, Bergman, RN, Bonnycastle, LL, Borch-Johnsen, K, Burtt, NP, Chen, H, Chines, PS, Daly, MJ, Deodhar, P, Ding, CJ, Doney, AS, Duren, WL, Elliott, KS, Erdos, MR, Frayling, TM, Freathy, RM, Gianniny, L, Grallert, H, Grarup, N, Groves, CJ, Guiducci, C, Hansen, T, Herder, C, Hitman, GA, Hughes, TE, Isomaa, B, Jackson, AU, Jørgensen, T, Kong, A, Kubalanza, K, Kuruvilla, FG, Kuusisto, J, Langenberg, C, Lango, H, Lauritzen, T, Li, Y, Lindgren, CM, Lyssenko, V, Marvelle, AF, Meisinger, C, Midthjell, K, Mohlke, KL, Morken, MA, Morris, AD, Narisu, N, Nilsson, P, Owen, KR, Palmer, CN, Payne, F, Perry, JR, Pettersen, E, Platou, C, Prokopenko, I, Qi, L, Qin, L, Rayner, NW, Rees, M, Roix, JJ, Sandbaek, A, Shields, B, Sjögren, M, Steinthorsdottir, V, Stringham, HM, Swift, AJ, Thorleifsson, G, Thorsteinsdottir, U, Timpson, NJ, Tuomi, T, Tuomilehto, J, Walker, M, Watanabe, RM, Weedon, MN, Willer, CJ, Wellcome Trust Case Control Consortium, Illig, T, Hveem, K, Hu, FB, Laakso, M, Stefansson, K, Pedersen, O, Wareham, NJ, Barroso, I, Hattersley, AT, Collins, FS, Groop, L, McCarthy, MI, Boehnke, M, Altshuler, D (2008). Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nature Genetics 40, 638–645.CrossRefGoogle ScholarPubMed