Je ne sais pas si tu as reservé ton intervention pour le bon moment (je blague bien sûr), mais le jour où tu as écris ce message, sort dans Nature les deux plus grosse études jamais réalisées sur ce thème.
Avec des résultats qui vont dans cette même direction, mais en affinant encore un peu (voire beaucoup, même).
Il y a une dizaine d'années, la schizophréine était un peu mystérieuse/mythique. Aujourd'hui, de moins en moins.
Nature. 2008 Jul 30; [Epub ahead of print]
Large recurrent microdeletions associated with schizophrenia.
Stefansson H, Rujescu D, Cichon S, Pietilainen 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, Moller 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, Muhleisen TW, Wang AG, Ullum H, Djurovic S, Melle I, Olesen J, Kiemeney LA, Franke B; Genetic Risk and Outcome in Psychosis (GROUP); Kahn RS, Linszen D, van Os J, Wiersma D, Bruggeman R, Cahn W, Germeys I, de Haan L, Krabbendam L, Sabatti C, Freimer NB, Gulcher JR, Thorsteinsdottir U, Kong A, Andreassen OA, Ophoff RA, Georgi A, Rietschel M, Werge T, Petursson H, Goldstein DB, Nothen MM, Peltonen L, Collier DA, St Clair D, Stefansson K.
[1] CNS Division, deCODE genetics, Sturlugata 8, IS-101 Reykjavik, Iceland [2] These authors contributed equally to this work.
Reduced fecundity, associated with severe mental disorders, places negative selection pressure on risk alleles and may explain, in part, why common variants have not been found that confer risk of disorders such as autism, schizophrenia and mental retardation. Thus, rare variants may account for a larger fraction of the overall genetic risk than previously assumed. In contrast to rare single nucleotide mutations, rare copy number variations (CNVs) can be detected using genome-wide single nucleotide polymorphism arrays. This has led to the identification of CNVs associated with mental retardation and autism. In a genome-wide search for CNVs associating with schizophrenia, we used a population-based sample to identify de novo CNVs by analysing 9,878 transmissions from parents to offspring. The 66 de novo CNVs identified were tested for association in a sample of 1,433 schizophrenia cases and 33,250 controls. Three deletions at 1q21.1, 15q11.2 and 15q13.3 showing nominal association with schizophrenia in the first sample (phase I) were followed up in a second sample of 3,285 cases and 7,951 controls (phase II). All three deletions significantly associate with schizophrenia and related psychoses in the combined sample. The identification of these rare, recurrent risk variants, having occurred independently in multiple founders and being subject to negative selection, is important in itself. CNV analysis may also point the way to the identification of additional and more prevalent risk variants in genes and pathways involved in schizophrenia.
PMID: 18668039 [PubMed - as supplied by publisher]
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Nature. 2008 Jul 30; [Epub ahead of print]
Rare chromosomal deletions and duplications increase risk of schizophrenia.
The International Schizophrenia Consortium ; Stone JL, O'Donovan MC, Gurling H, Kirov GK, Blackwood DH, Corvin A, Craddock NJ, Gill M, Hultman CM, Lichtenstein P, McQuillin A, Pato CN, Ruderfer DM, Owen MJ, St Clair D, Sullivan PF, Sklar P, Purcell Leader SM; Data analysis; Stone JL, Ruderfer DM, Korn J, Kirov GK, Macgregor S, McQuillin A, Morris DW, O'Dushlaine CT, Daly MJ, Visscher PM, Holmans PA, O'Donovan MC, Sullivan PF, Sklar P, Purcell Leader SM; Management committee; Gurling H, Corvin A, Blackwood DH, Craddock NJ, Gill M, Hultman CM, Kirov GK, Lichtenstein P, McQuillin A, O'Donovan MC, Owen MJ, Pato CN, Purcell SM, Scolnick EM, St Clair D, Stone JL, Sullivan PF, Sklar Leader P; Cardiff University; O'Donovan MC, Kirov GK, Craddock NJ, Holmans PA, Williams NM, Georgieva L, Nikolov I, Norton N, Williams H, Toncheva D, Milanova V, Owen MJ; Karolinska Institutet/University of North Carolina at Chapel Hill; Hultman CM, Lichtenstein P, Thelander EF, Sullivan P; Trinity College Dublin; Morris DW, O'Dushlaine CT, Kenny E, Waddington JL, Gill M, Corvin A; University College London; McQuillin A, Choudhury K, Datta S, Pimm J, Thirumalai S, Puri V, Krasucki R, Lawrence J, Quested D, Bass N, Curtis D, Gurling H; University of Aberdeen; Crombie C, Fraser G, Leh Kwan S, Walker N, St Clair D; University of Edinburgh; Blackwood DH, Muir WJ, McGhee KA, Pickard B, Malloy P, Maclean AW, Van Beck M; Queensland Institute of Medical Research; Visscher PM, Macgregor S; University of Southern California; Pato MT, Medeiros H, Middleton F, Carvalho C, Morley C, Fanous A, Conti D, Knowles JA, Paz Ferreira C, Macedo A, Helena Azevedo M, Pato CN; Massachusetts General Hospital; Stone JL, Ruderfer DM, Korn J, McCarroll SA, Daly M, Purcell SM, Sklar P; Stanley Center for Psychiatric Research and Broad Institute of MIT and Harvard; Purcell SM, Stone JL, Chambert K, Ruderfer DM, Korn J, McCarroll SA, Gates C, Gabriel SB, Mahon S, Ardlie K, Daly MJ, Scolnick EM, Sklar P.
[1] Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, 185 Cambridge Street, Boston, Massachusetts 02114, USA. [2] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA. [3] Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA. [4] Center for Human Genetic Research, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA.
Schizophrenia is a severe mental disorder marked by hallucinations, delusions, cognitive deficits and apathy, with a heritability estimated at 73-90% (ref. 1). Inheritance patterns are complex, and the number and type of genetic variants involved are not understood. Copy number variants (CNVs) have been identified in individual patients with schizophrenia and also in neurodevelopmental disorders, but large-scale genome-wide surveys have not been performed. Here we report a genome-wide survey of rare CNVs in 3,391 patients with schizophrenia and 3,181 ancestrally matched controls, using high-density microarrays. For CNVs that were observed in less than 1% of the sample and were more than 100 kilobases in length, the total burden is increased 1.15-fold in patients with schizophrenia in comparison with controls. This effect was more pronounced for rarer, single-occurrence CNVs and for those that involved genes as opposed to those that did not. As expected, deletions were found within the region critical for velo-cardio-facial syndrome, which includes psychotic symptoms in 30% of patients. Associations with schizophrenia were also found for large deletions on chromosome 15q13.3 and 1q21.1. These associations have not previously been reported, and they remained significant after genome-wide correction. Our results provide strong support for a model of schizophrenia pathogenesis that includes the effects of multiple rare structural variants, both genome-wide and at specific loci.
