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News Brief: Common Variant for Psychosis Fingered at 16p11.2

24 December 2012. A common variant at 16p11.2 increases risk of psychosis, according to a report published online November 20 in Molecular Psychiatry. Led by Kari Stefansson of deCODE Genetics in Reykjavik, Iceland, the study combined cases of schizophrenia, bipolar disorder, and other psychoses to search for variants related to psychosis, rather than to a specific diagnosis. The results flag a single nucleotide polymorphism (SNP) within a 593 kb region that has been previously linked to schizophrenia and other disorders by rare copy number variants (CNVs).

The findings build on their previous schizophrenia GWAS, which identified 39 single nucleotide polymorphisms (SNPs) that, though not genomewide-significant hits, had promising p values (see SRF related news story). In the new study, the researchers surveyed these same SNPs in an enlarged dataset, consisting of 27,543 cases with psychosis and 88,696 controls. A SNP at 16p11.2 attained genomewide significance (p = 6.6 x 10-11), with an odds ratio of 1.08, and suggests that combining diagnoses does not necessarily dilute psychosis-related GWAS signals.

The SNP lies in a region already on the radar: duplications are associated with schizophrenia, bipolar disorder, autism, and microcephaly, whereas deletions are associated with autism, developmental delay, and macrocephaly (see SRF related news story). Though a recent zebrafish study identified the KCTD13 gene in this region as controlling head size (see SRF related news story), the new study did not find that the SNP altered this gene’s expression in human brain tissue. They did, however, report an association between the SNP and expression of MAPK3, a gene that modified zebrafish head size in combination with KCTD13.—Michele Solis.

Steinberg S, de Jong S, Mattheisen M, Costas J, Demontis D, Jamain S, Pietiläinen OP, Lin K, Papiol S, Huttenlocher J, Sigurdsson E, Vassos E, Giegling I, Breuer R, Fraser G, Walker N, Melle I, Djurovic S, Agartz I, Tuulio-Henriksson A, Suvisaari J, Lönnqvist J, Paunio T, Olsen L, Hansen T, Ingason A, Pirinen M, Strengman E; GROUP, Hougaard DM, Orntoft T, Didriksen M, Hollegaard MV, Nordentoft M, Abramova L, Kaleda V, Arrojo M, Sanjuán J, Arango C, Etain B, Bellivier F, Méary A, Schürhoff F, Szoke A, Ribolsi M, Magni V, Siracusano A, Sperling S, Rossner M, Christiansen C, Kiemeney LA, Franke B, van den Berg LH, Veldink J, Curran S, Bolton P, Poot M, Staal W, Rehnstrom K, Kilpinen H, Freitag CM, Meyer J, Magnusson P, Saemundsen E, Martsenkovsky I, Bikshaieva I, Martsenkovska I, Vashchenko O, Raleva M, Paketchieva K, Stefanovski B, Durmishi N, Pejovic Milovancevic M, Lecic Tosevski D, Silagadze T, Naneishvili N, Mikeladze N, Surguladze S, Vincent JB, Farmer A, Mitchell PB, Wright A, Schofield PR, Fullerton JM, Montgomery GW, Martin NG, Rubino IA, van Winkel R, Kenis G, De Hert M, Réthelyi JM, Bitter I, Terenius L, Jönsson EG, Bakker S, van Os J, Jablensky A, Leboyer M, Bramon E, Powell J, Murray R, Corvin A, Gill M, Morris D, O'Neill FA, Kendler K, Riley B; Wellcome Trust Case Control Consortium 2, Craddock N, Owen MJ, O'Donovan MC, Thorsteinsdottir U, Kong A, Ehrenreich H, Carracedo A, Golimbet V, Andreassen OA, Børglum AD, Mors O, Mortensen PB, Werge T, Ophoff RA, Nöthen MM, Rietschel M, Cichon S, Ruggeri M, Tosato S, Palotie A, St Clair D, Rujescu D, Collier DA, Stefansson H, Stefansson K. Common variant at 16p11.2 conferring risk of psychosis. Mol Psychiatry. 2012 Nov 20. Abstract

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