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News Brief: Inherited Duplication Ups Psychosis Risk

February 10, 2014. Duplications at chromosome 20p12.2 increase risk for schizophrenia and bipolar disorder with psychosis, according to a report published online January 28 in Human Molecular Genetics. As SRF reported when the study was presented at the 2012 World Congress of Psychiatric Genetics (see SRF related news report), this locus adds to the roster of rare copy number variations (CNVs) that increase risk for schizophrenia. Unlike many of these, however, the 146.5 kilobase duplication is inherited, and seems specific for psychosis.

Led by Aiden Corvin of Trinity College Dublin, Ireland, and Chris Spencer of the University of Oxford, UK, the study drew from largely European samples to peg the odds ratio of the duplication at 11.3. The duplication contains a gene called p21 protein-activated kinase 7 (PAK7), which is exclusively expressed in brain and promotes neurite outgrowth and synapse development. The researchers also found that PAK7 interacted with the known risk gene disrupted in schizophrenia 1 (DISC1), and they suggest that the duplication alters early neural development in a way that leaves the brain at risk for psychosis.—Michele Solis.

Morris DW, Pearson RD, Cormican P, Kenny EM, O'Dushlaine CT, Lemieux Perreault LP, Giannoulatou E, Tropea D, Maher BS,Wormley B, Kelleher E, Fahey C, Molinos I, Bellini S, Pirinen M, Strange A, Freeman C, Thiselton DL, Elves RL, Regan R, Ennis S,Dinan TG, McDonald C, Murphy KC, O'Callaghan E, Waddington JL, Walsh D, O'Donovan M, Grozeva D, Craddock N, Stone J, Scolnick E, Purcell S, Sklar P, Coe B, Eichler EE, Ophoff R, Buizer J, Szatkiewicz J, Hultman C, Sullivan P, Gurling H, McQuillin A, St Clair D,Rees E, Kirov G, Walters J, Blackwood D, Johnstone M, Donohoe G; International Schizophrenia Consortium; SGENE+ Consortium,O'Neill FA; Wellcome Trust Case Control Consortium 2, Kendler KS, Gill M, Riley BP, Spencer CC, Corvin A. An inherited duplication at the gene p21 Protein-Activated Kinase 7 (PAK7) is a risk factor for psychosis. Hum Mol Genet. 2014 Jan 28. Abstract

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