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Nat Neurosci. 2014 Jun;17(6):782-90. doi: 10.1038/nn.3708. Epub 2014 May 27.

Large-scale genomics unveils the genetic architecture of psychiatric disorders.

Author information

1
1] Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia. [2] These authors contributed equally to this work.
2
1] Department of Psychology and Neuroscience, University of Colorado, Boulder, Colorado, USA. [2] These authors contributed equally to this work.
3
1] Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia. [2] The Translational Research Institute, University of Queensland Diamantina Institute, Brisbane, Queensland, Australia. [3] These authors contributed equally to this work.

Abstract

Family study results are consistent with genetic effects making substantial contributions to risk of psychiatric disorders such as schizophrenia, yet robust identification of specific genetic variants that explain variation in population risk had been disappointing until the advent of technologies that assay the entire genome in large samples. We highlight recent progress that has led to a better understanding of the number of risk variants in the population and the interaction of allele frequency and effect size. The emerging genetic architecture implies a large number of contributing loci (that is, a high genome-wide mutational target) and suggests that genetic risk of psychiatric disorders involves the combined effects of many common variants of small effect, as well as rare and de novo variants of large effect. The capture of a substantial proportion of genetic risk facilitates new study designs to investigate the combined effects of genes and the environment.

PMID:
24866044
PMCID:
PMC4112149
DOI:
10.1038/nn.3708
[Indexed for MEDLINE]
Free PMC Article

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