Browsing by Author "Visscher, P. M."
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- Common polygenic variation contributes to risk of schizophrenia and bipolardisorderPublication . Purcell, S. M.; Wray, N. R.; Stone, J. L.; Visscher, P. M.; O'Donovan, M. C.; Sullivan, P. F.; Sklar, P.; Leader, S. M.; Ruderfer, D. M.; McQuillin, A.; Morris, D. W.; O'Dushlaine, C. T.; Corvin, A.; Holmans, P. A.; Macgregor, S.; Gurling, H.; Blackwood, D. H.; Craddock, N. J.; Gill, M.; Hultman, C. M.; Kirov, G. K.; Lichtenstein, P.; Muir, W. J.; Owen, M. J.; Pato, Carlos N.; Scolnick, E. M.; St Clair, D.; Williams, N. M.; Georgieva, L.; Nikolov, I.; Norton, N.; Williams, H.; Toncheva, D.; Milanova, V.; Helander, E. F.; Kenny, E.; Quinn, E. M.; Choudhury, K.; Datta, S.; Pimm, J.; Thirumalai, S.; Puri, V.; Krasucki, R.; Lawrence, J.; Quested, D.; Bass, N.; Crombie, C.; Fraser, G.; Leh, K. S.; Walker, N.; Black-wood, D. H.; McGhee, K. A.; Pickard, B.; Malloy, P.; Maclean, A. W.; Van Beck, M.; Pato, Michele T.; Medeiros, Helena; Middleton, Frank A.; Carvalho, Célia; Morley, C.; Fanous, Ayman H.; Conti, D.; Knowles, James A.; Ferreira, Carlos Paz; Macedo, António; Kirby, A. N.; Ferreira, M. A.; Daly, M. J.; Cham-bert, K.; Kuruvilla, F.; Gabriel, S. B.; Ardlie, K.; Moran, J. L.Schizophrenia is a severe mental disorder with a lifetime risk of about 1%, characterized by hallucinations, delusions and cognitive deficits, with heritability estimated at up to 80%. We performed a genome-wide association study of 3,322 European individuals with schizophrenia and 3,587 controls. Here we show, using two analytic approaches, the extent to which common genetic variation underlies the risk of schizophrenia. First, we implicate the major histocompatibility complex. Second, we provide molecular genetic evidence for a substantial polygenic component to the risk of schizophrenia involving thousands of common alleles of very small effect. We show that this component also contributes to the risk of bipolar disorder, but not to several non-psychiatric diseases.
- Rare chromosomal deletions and duplications increase risk of schizophreniaPublication . Craddock, N. J.; Gill, M.; Hultman, C. M.; Lichtenstein, P.; McQuillin, A.; Pato, Carlos N.; Ruderfer, D. M.; Owen, M. J.; St Clair, David; Sullivan, P. F.; Sklar, P.; Purcell, S. M.; Stone, J. L; Korn, Joshua; Macgregor, S.; Morris, D. W.; O'Dushlaine, C. T.; Daly, M. J.; Visscher, P. M.; Holmans, P. A.; Scolnick, E: M.; Williams, N. M.; Georgieva, L.; Nikolov, I.; Norton, N.; Williams, H.; Toncheva, D.; Milanova, V.; Thelander, Emma F.; Sullivan, P. F.; Kenny, E.; Waddington, John L.; Choudhury, K.; Datta, S.; Pimm, J.; Thirumalai, S.; Puri, V.; Krasucki, R.; Lawrence, J.; Quested, D.; Bass, N.; Curtis, David; Gurling, H.; Crombie, C.; Fraser, G.; Kwan, Soh Leh; Walker, N.; Muir, W. J.; McGhee, K. A.; Pickard, B.; Malloy, P.; Maclean, A. W.; Van Beck, Margaret; Visscher, P. M.; Pato, Michele T.; Medeiros, Helena; Middleton, Frank A.; Carvalho, Célia; Morley, C.; Fanous, Ayman H.; Conti, D.; Knowles, James A.; Ferreira, Carlos Paz; Macedo, António; Azevedo, Maria H.; McCarroll, Steve A.; Daly, M. J.; Chambert, Kimberly; Gates, CaseySchizophrenia 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 (12). 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.