Ditte Demontis

Genome-wide association study identifies five new schizophrenia loci

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

  • Stephan Ripke
  • ,
  • Alan R Sanders
  • ,
  • Kenneth S Kendler
  • ,
  • Douglas F Levinson
  • ,
  • Pamela Sklar
  • ,
  • Peter A Holmans
  • ,
  • Dan-Yu Lin
  • ,
  • Jubao Duan
  • ,
  • Roel A Ophoff
  • ,
  • Ole A Andreassen
  • ,
  • Edward Scolnick
  • ,
  • Sven Cichon
  • ,
  • David St Clair
  • ,
  • Aiden Corvin
  • ,
  • Hugh Gurling
  • ,
  • Thomas Werge
  • ,
  • Dan Rujescu
  • ,
  • Douglas H R Blackwood
  • ,
  • Carlos N Pato
  • ,
  • Anil K Malhotra
  • ,
  • Shaun Purcell
  • ,
  • Frank Dudbridge
  • ,
  • Benjamin M Neale
  • ,
  • Lizzy Rossin
  • ,
  • Peter M Visscher
  • ,
  • Danielle Posthuma
  • ,
  • Douglas M Ruderfer
  • ,
  • Ayman Fanous
  • ,
  • Hreinn Stefansson
  • ,
  • Stacy Steinberg
  • ,
  • Bryan J Mowry
  • ,
  • Vera Golimbet
  • ,
  • Marc De Hert
  • ,
  • Erik G Jönsson
  • ,
  • István Bitter
  • ,
  • Olli P H Pietiläinen
  • ,
  • David A Collier
  • ,
  • Sarah Tosato
  • ,
  • Ingrid Agartz
  • ,
  • Margot Albus
  • ,
  • Madeline Alexander
  • ,
  • Richard L Amdur
  • ,
  • Farooq Amin
  • ,
  • Nicholas Bass
  • ,
  • Anders D Børglum
  • Ditte Demontis
  • Ole Mors
  • Preben B Mortensen
  • Jimmi Nielsen, Danmark
  • Torben F Orntoft
  • The Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium
We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 × 10(-11)) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 × 10(-9)), ANK3 (rs10994359, P = 2.5 × 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10(-9)).
OriginalsprogEngelsk
TidsskriftNature Genetics
Vol/bind43
Nummer10
Sider (fra-til)969-976
Antal sider8
ISSN1061-4036
DOI
StatusUdgivet - 1 jan. 2011

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