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Author Notes:

Correspondence and requests for materials should be addressed to Michael O’Donovan: odonovanmc@cardiff.ac.uk or odonovanmc@cf.ac.uk

See publication for full list of authors and contributions.

We thank Dr Thomas Lehner (NIMH). The work of the contributing groups was supported by numerous grants from governmental and charitable bodies as well as philanthropic donation.

Several of the authors are employees of the following pharmaceutical companies; Pfizer (C.R.S., J.R.W., H.S.X.), F. Hoffman-La Roche (E.D., L.E.), Eli Lilly (D.A.C., Y.M., L.N.) and Janssen (S.G., D.W., Q.S.L.; also N.C. an ex-employee).

Others are employees of deCODE genetics (S.S., H.S., K.S.).

None of these companies influenced the design of the study, the interpretation of the data, the amount of data reported, or financially profit by publication of the results which are pre-competitive.

The other authors declare no competing interests.

Subject:

Research Funding:

Core funding for the Psychiatric Genomics Consortium is from the US National Institute of Mental Health (U01 MH094421).

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • GENOME-WIDE ASSOCIATION
  • COMMON VARIANTS
  • CONFERRING RISK
  • MUTATIONS

Biological insights from 108 schizophrenia-associated genetic loci

Journal Title:

NATURE

Volume:

Volume 511, Number 7510

Publisher:

, Pages 421-+

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.

Copyright information:

© 2014 Macmillan Publishers Limited. All rights reserved.

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