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Access through your institution Buy or subscribe In setting out their framework for interpreting genome-wide association studies of psychiatric disorders,1 the Psychiatric GWAS Consortium

Steering Committee considers all possible outcomes ranging from the most favorable (‘psychiatric’ equivalents to association between fat mass and obesity associated (_FTO_) variants and body

mass index), through to the least, that the common disease/common variants (CDCV) hypothesis predicated by the GWAS-study design is flawed. This laudable and transparent synopsis of what

may or may not emerge from costly GWAS mega-analyses raises conceptual and practical issues that bear comment. The CDCV model of psychiatric disease is founded on the multifactorial

threshold model of risk for disease2 and assumes that disease arises from the co-inheritance of multiple risk variants, each of small individual effect. To explain the population prevalence,

such variants must themselves be common and should therefore be detectable by GWAS.3 This model assumes that liability is normally distributed in the population. To explain how a

discontinuous trait such as a psychiatric diagnosis can emerge from such a distribution, a threshold of liability (of unspecified origin) is invoked, with those individuals above being at

high and those below at low risk of the disease. This statistical sleight of hand allows the powerful statistics of normal distributions to be applied, but how strong is this conceptual

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are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES * PGC. _Mol Psychiatry_

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Genetics, Trinity College, Dublin, Ireland K J Mitchell * Medical Genetics Section, Institute of Genetics and Molecular Medicine, University of Edinburgh Molecular Medicine Centre,

Edinburgh, UK D J Porteous Authors * K J Mitchell View author publications You can also search for this author inPubMed Google Scholar * D J Porteous View author publications You can also

search for this author inPubMed Google Scholar CORRESPONDING AUTHORS Correspondence to K J Mitchell or D J Porteous. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE

THIS ARTICLE Mitchell, K., Porteous, D. GWAS for psychiatric disease: is the framework built on a solid foundation?. _Mol Psychiatry_ 14, 740–741 (2009). https://doi.org/10.1038/mp.2009.17

Download citation * Published: 23 July 2009 * Issue Date: August 2009 * DOI: https://doi.org/10.1038/mp.2009.17 SHARE THIS ARTICLE Anyone you share the following link with will be able to

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