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Mol Psychiatry. 2015 May;20(5):555-62. doi: 10.1038/mp.2015.16. Epub 2015 Mar 10.

Evaluating historical candidate genes for schizophrenia.

Author information

1
Center for Psychiatric Genomics, Department of Genetics, Genomic Medicine, University of North Carolina, Chapel Hill, NC, USA.
2
1] Institute of Biological Psychiatry, MHC Sct. Hans, Mental Health Services Copenhagen, Denmark [2] Department of Clinical Medicine, University of Copenhagen, Copenhagen, Aarhus, Denmark [3] The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
3
1] Division of Psychiatric Genomics, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA [2] Institute for Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA [3] Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
4
1] MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK [2] National Centre for Mental Health, Cardiff University, Cardiff, UK.
5
1] Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA [2] Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA [3] Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, The Netherlands.
6
Neuropsychiatric Genetics Research Group, Department of Psychiatry, Trinity College Dublin, Ireland.
7
1] Division of Medical Genetics, Department of Biomedicine, University Basel, Basel, Switzerland [2] Institute of Human Genetics, University of Bonn, Bonn, Germany [3] Department of Genomics, Life and Brain Center, Bonn, Germany.
8
1] Center for Psychiatric Genomics, Department of Genetics, Genomic Medicine, University of North Carolina, Chapel Hill, NC, USA [2] Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden [3] Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.

Abstract

Prior to the genome-wide association era, candidate gene studies were a major approach in schizophrenia genetics. In this invited review, we consider the current status of 25 historical candidate genes for schizophrenia (for example, COMT, DISC1, DTNBP1 and NRG1). The initial study for 24 of these genes explicitly evaluated common variant hypotheses about schizophrenia. Our evaluation included a meta-analysis of the candidate gene literature, incorporation of the results of the largest genomic study yet published for schizophrenia, ratings from informed researchers who have published on these genes, and ratings from 24 schizophrenia geneticists. On the basis of current empirical evidence and mostly consensual assessments of informed opinion, it appears that the historical candidate gene literature did not yield clear insights into the genetic basis of schizophrenia. A likely reason why historical candidate gene studies did not achieve their primary aims is inadequate statistical power. However, the considerable efforts embodied in these early studies unquestionably set the stage for current successes in genomic approaches to schizophrenia.

PMID:
25754081
PMCID:
PMC4414705
DOI:
10.1038/mp.2015.16
[Indexed for MEDLINE]
Free PMC Article

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