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Peer review: Brain genetics paper on schizophrenia retracted

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From The Scientist :

The now-retracted study identified a set of gene ontologies (GO) associated with a brain phenotype that has been previously shown to be disturbed in patients with schizophrenia. Andreas Meyer-Lindenberg, director of the Central Institute of Mental Health Mannheim, Germany, and his colleagues had healthy volunteers perform a working memory task known to require communication between the hippocampus and the prefrontal cortex while scanning their brains using functional magnetic resonance imaging (fMRI). The volunteers also underwent whole-genome genotyping. Combining the fMRI and genomic data, the researchers identified groups of genes that appeared associated with communication between the two brain regions, which can be disturbed in some people with schizophrenia. The authors used gene set enrichment analysis to pick out genes associated with this brain phenotype, identifying 23 that could be involved in the pathology of the brain disorder.

The Scientist first learned of possible problems with this analysis when the paper was under embargo prior to publication. At that time, The Scientist contacted Paul Pavlidis, a professor of psychiatry at the University of British Columbia who was not connected to the work, for comment on the paper. He pointed out a potential methodological flaw that could invalidate its conclusions. After considering the authors’ analyses, Pavlidis reached out to Meyer-Lindenberg’s team to discuss the statistical issues he perceived.

The original analysis flagged a set of 11 genes in close proximity to one another within the genome using the same single nucleotide polymorphism (SNP), inflating the significance of the results. More.


Elizabeth Thomas, who studies the molecular mechanisms of neurological disorders at The Scripps Research Institute in La Jolla, California, and was not involved in the work noted that the GO annotations used in the study were outdated. “GOs change every few months, and it’s unfortunate for researchers that rely on a certain set of annotations. It makes you wonder whether the papers published in the past five to 10 years are still relevant,” said Thomas. “This retraction raises the issue of how many papers may have falsely reported gene associations because of the constantly evolving changes in gene assemblies and boundaries. That’s really alarming to me.”

Schizophrenia is perhaps the most maddening of the mental illnesses, in all senses.

On the bright side, this seems to have been a responsible, back-to-the-drawing-board, retraction. One we can learn from.

(By contrast, we can’t learn anything from fraud in science except that fraud is bad for science, but we knew that, right?)

Note: Schizophrenia claimed the life of a friend many years ago, by suicide. Requiescat in pacem lucis aeternitatis, numquam oblita– O’Leary for News


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