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Lien YJ, Liu CM, Faraone SV, Tsuang MT, Hwu HG, Hsiao PC, Chen WJ. A genome-wide quantitative trait loci scan of neurocognitive performances in families with schizophrenia. Genes Brain Behav . 2010 Oct ; 9(7):695-702. PubMed Abstract

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Comment by:  Timothea Toulopoulou
Submitted 8 July 2010 Posted 8 July 2010

Although schizophrenia has a high heritability, the genetic effects conferring risk to schizophrenia are complex and comprise multifactorial polygenic inheritance. “Endophenotypes” are often synonymous with cognitive and brain deviations, are hypothetically narrower constructs of genetic risk, and are assumed to be closer to the gene effects in the disease pathway than the clinical phenotypes. Lien and colleagues used this familiar strategy of endophenotypes (Toulopoulou et al., 2007; Owens et al., 2010) to perform a series of genomewide QTL linkage scans in a large sample of Han Chinese families with schizophrenia. QTL genomewide scans identified 12q24.32 as a novel linkage region for conferring susceptibility to a single index of sustained attention deficit (undegraded CPT hit rate) in patients with schizophrenia. The highest linkage signal identified in this study (NPL-Z scores of 3.32 on 12q24.32) was greater than that in their original linkage study using a dichotomous disease...  Read more

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Comment by:  Anna Need
Submitted 12 July 2010 Posted 12 July 2010

It was an interesting approach by Lien et al. to perform a linkage study on neurocognitive performance in schizophrenia families, and they describe a valuable cohort. Unfortunately, as the authors acknowledge, given the margin of significance (p = 0.03) and the number of tests performed, it is difficult to see this is anything other than a false positive (only the different genetic markers were corrected for, not the multiple phenotypes). False positives have plagued the world of schizophrenia genetics, and it doesn’t seem unreasonable to require that linkage (and association) results are confirmed in a replication cohort before they are published.

View all comments by Anna Need

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