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Flawed Analysis

German scientists have retracted a recent paper in which they claimed to have identified sets of genes that are associated with a brain phenotype that has been linked to schizophrenia.

The authors say the conclusions they drew from the study, which they published in June in PNAS, were based on flawed statistical analysis. Anna Azvolinsky writes in The Scientist.

Andreas Meyer-Lindenberg, director of the Central Institute of Mental Health in Mannheim, Germany, and colleagues had volunteers perform a memory task cortex while their brains were scanned with functional MRI. They also underwent whole-genome genotyping. By examining fMRI and genomic data, the authors identified groups of genes that appear to be involved in communication between the hippocampus and prefrontal cortex, both areas that can be impacted by schizophrenia. By analyzing their results, the investigators identified 23 genes they said could be involved in the pathology behind schizophrenia.

But there was a problem. The analysis flagged a set of 11 genes that are close to the other by targeting the same SNP.

"The researchers found a variant near a genomic region that they say is correlated with the [working memory] task," says Paul Pavlidis, a professor at the University of British Columbia who is not involved in the study.
"But instead of counting that variant once, that variant was counted 11 times."

"When we re-analyzed the data, we saw that we had to retract because addressing the problem went beyond just an erratum,” Meyer-Lindenberg says.

Pavlidis says the authors did the right thing by pulling the paper when the error came to light, but the incident may bring up a larger problem.

"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," Elizabeth Thomas, of the Scripps Research Institute, tells The Scientist. "It makes you wonder whether the papers published in the past five to 10 years are still relevant."