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, Smoller JW, Craddock N, Kendler K, Lee PH, Neale BM, Nurnberger JI, Ripke S, Santangelo S, Sullivan PF. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet . 2013 Apr 20 ; 381(9875):1371-9. PubMed Abstract

Comments on Paper and Primary News
Comment by:  Laura Almasy
Submitted 5 March 2013 Posted 5 March 2013

This is a very important paper. Just a few years ago, the idea of shared genetic effects across psychiatric disorders was virtual heresy. This study provides empirical evidence to help us move past our biases and consider new hypotheses. These results also support the importance of identifying and studying phenotypes that tap into the layers of function between genes and diagnoses, and may help us to understand what is shared across disorders and what may be unique.

View all comments by Laura Almasy

Comment by:  Francis McMahon, SRF Advisor
Submitted 5 March 2013 Posted 5 March 2013

This very important study provides a broader context for the 2009 finding from the International Schizophrenia Consortium (ISC) that schizophrenia and bipolar disorder overlap substantially in terms of common risk allele burden. Now we see that this overlap extends not only to depression (as shown previously by Schulze et al., 2012), but also to autism and ADHD. This study could only have been accomplished with strong cooperation among many groups, and its success is a testament to the cooperative approach of the Psychiatric Genomics Consortium (PGC).

What does it all mean? Perhaps common alleles are not really the seeds of psychiatric disorders, but rather the soil in which those seeds take root? Could the expression of particular symptoms depend largely on non-genetic factors? Or are common alleles—which account for only about 5 percent of the observed phenotypic variance—too blunt an instrument for parsing the numerous combinations of genetic risk factors that underlie mental illnesses? We need to understand more about the...  Read more

View all comments by Francis McMahon

Comment by:  Ben Pickard
Submitted 6 March 2013 Posted 6 March 2013

Smoller et al., comprising the Cross-Disorder group of the Psychiatric Genomics Consortium, present clear evidence to support a small, but statistically significant, component of genetic susceptibility that is shared among the major neuropsychiatric disorders.

The authors discuss the disconnect between the discrete diagnostic boundaries currently used to partition individuals in a healthcare setting and these new findings that indicate a blurring of such distinctions. This is not a unique observation. The overlap of genes in inflammatory disorders is described by Smoller, and MAPT, the tau protein gene, may also be a useful reference point. It is involved in tangles of Alzheimer’s pathology, Parkinson’s disorder risk, as well as participating in a number of other degenerative disorders such as progressive supranuclear palsy, Pick’s disease, and frontotemporal lobar degeneration.

The implicit assumption in the current study is that there must be universal biological processes driven by these common risk genes that impact on disorders ranging from ADHD to schizophrenia....  Read more

View all comments by Ben Pickard
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