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Annotation

Fowler T, Zammit S, Owen MJ, Rasmussen F. A population-based study of shared genetic variation between premorbid IQ and psychosis among male twin pairs and sibling pairs from Sweden. Arch Gen Psychiatry . 2012 May ; 69(5):460-6. PubMed Abstract

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Comment by:  James MacCabe
Submitted 29 May 2012 Posted 29 May 2012

The endophenotype approach to studying the genetics of psychosis relies on a shared genetic origin between the endophenotype in question and the psychosis phenotype. This is usually inferred by the presence of impairments in the unaffected relatives of patients. However, population-based studies including information on relatedness, the putative endophenotype, and the psychosis phenotype offer the opportunity to test this association at the population level. In the first such study, Fowler and colleagues set out to examine the relationship between genetic influences in premorbid IQ and psychosis in a Swedish longitudinal, population-based study. Genetic relatedness was taken from the Swedish Multigeneration Register and Twin Registry, allowing the identification of pairs of MZ and DZ twins and sibling pairs with an age gap no greater than five years. A proxy for IQ was taken from the Military Conscription Register (thus restricting the analysis to males), and the psychosis phenotype from the Hospital Discharge Register.

In agreement with previous studies (  Read more


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Comment by:  Timothea Toulopoulou
Submitted 1 October 2012 Posted 1 October 2012

Objections are principled but not data driven
Fowler and colleagues (Fowler et al., 2012) should be warmly congratulated on their study examining the relationship between IQ and psychotic disorders in a population-based cohort. Fowler’s excellent study addresses in a superior design some of the limitations that we recognized in our previous studies (Toulopoulou et al., 2007; Toulopoulou et al., 2010). We are therefore very grateful to them for their contribution.

However, there are a number of reasons that might suggest that the interpretations of Fowler et al. are overstated. For example, dismissing a phenotypic correlation of -0.22 between premorbid IQ and psychosis, when most of this appears to relate to shared genetic covariance, is, in my opinion, an omission. Specifically, discarding up to 14 percent of net shared genetic influences between IQ and psychosis—when the effect sizes for our best candidate risk...  Read more


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