Journal article
Evidence-based psychiatric genetics, AKA the false dichotomy between common and rare variant hypotheses
PM Visscher, ME Goddard, EM Derks, NR Wray
Molecular Psychiatry | Published : 2012
DOI: 10.1038/mp.2011.65
Abstract
In this article, we review some of the data that contribute to our understanding of the genetic architecture of psychiatric disorders. These include results from evolutionary modelling (hence no data), the observed recurrence risk to relatives and data from molecular markers. We briefly discuss the common-disease common-variant hypothesis, the success (or otherwise) of genome-wide association studies, the evidence for polygenic variance and the likely success of exome and whole-genome sequencing studies. We conclude that the perceived dichotomy between 'common' and 'rare' variants is not only false, but unhelpful in making progress towards increasing our understanding of the genetic basis of..
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Awarded by Australian Research Council
Funding Acknowledgements
We acknowledge funding from the Australian National Health and Medical Research Council (Grants 389892, 442915, 496688, 613672 and 613601) and the Australian Research Council (Grants DP0770096 and DP1093900 and Future Fellowship to NRW). We thank Adam Eyre-Walker for discussions and correspondence regarding computing Zeta functions, and Bill Hill for helpful comments. We dedicate this paper to the memory of Charlie Smith and Douglas Falconer, who had it all worked out 40 years ago.