Hyman SE. 2018. The daunting polygenicity of mental illness: making a new map. Philosophical transactions of the Royal Society of London. Series B, Biological sciences. 373(1742). Pubmed: 29352030 DOI:10.1098/rstb.2017.0031


An epochal opportunity to elucidate the pathogenic mechanisms of psychiatric disorders has emerged from advances in genomic technology, new computational tools and the growth of international consortia committed to data sharing. The resulting large-scale, unbiased genetic studies have begun to yield new biological insights and with them the hope that a half century of stasis in psychiatric therapeutics will come to an end. Yet a sobering picture is coming into view; it reveals daunting genetic and phenotypic complexity portending enormous challenges for neurobiology. Successful exploitation of results from genetics will require eschewal of long-successful reductionist approaches to investigation of gene function, a commitment to supplanting much research now conducted in model organisms with human biology, and development of new experimental systems and computational models to analyse polygenic causal influences. In short, psychiatric neuroscience must develop a new scientific map to guide investigation through a polygenic This article is part of a discussion meeting issue 'Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'.
© 2018 The Authors.

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Steven Hyman is Director of the Stanley Center for Psychiatric Research at the Broad Institute and Chair of the Schizophrenia Spectrum Biomarkers Consortium (SSBC), a consortium identifying objective biomarkers to enable better diagnosis of and treatment for schizophrenia and related illnesses.

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