Brain Genetics Paper Retracted

Sep 5, 2014

By Anna Azvolinsky

 

The authors of a June PNAS paper that purported to identify sets of genes associated with a specific brain function last week (August 29) retracted the work because of flaws in their statistical analyses. “We feel that the presented findings are not currently sufficiently robust to provide definitive support for the conclusions of our paper, and that an extensive reanalysis of the data is required,” the authors wrote in their retraction notice.

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. “The researchers found a variant near a genomic region that they say is correlated with the [working memory] task,” explained Pavlidis. “But instead of counting that variant once, that variant was counted 11 times.”

13 comments on “Brain Genetics Paper Retracted

  • This illustrates the difference between peer-reviewed science, and religious of pseudo-science claims. Science retracts claims where there is insufficient or inconclusive evidence!
    Theologians and pseudo-scientists cling to anything which lends credence to their preconceptions.



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  • Thank goodness some scientists are still rising above the social trend and accepting that it is possible for their work to be faulty.

    To me this is the mark of true professionals, people who are so concerned with being real that they will pull in all their work of many months and look again.

    How humble. How honest. How heroic.



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  • I get choked up about this too. This attitude changed everything and unlocked the reliable power of scientific thinking.

    It might be a plan (at least in a popular science magazine) to celebrate these self effacing acts at the end of each year and (just for fun) prioritise them by apparent bravery, (how much work compromised etc.). Get people to offer some comments on how their new insights came about and how it affected them. These acts cost. It would be nice to pay back a little.



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  • I’m reading a book by Michael Brooks at the moment ‘Free Radicals’. He is kind of celebrating the chaos in science, people going with hunches and fudging the data etc. I haven’t finished reading it but so far I’m unimpressed by his main argument.

    I’m not disagreeing with the cases of fraud or exaggeration he mentions mind, but the fact that we know about them is because the process of science has done its thing, correcting for errors building and modifying data. To me Bronowski said it best “science is a testament to what we can understand in-spite of being fallible”. The mistake is made when we give too much credence to the scientist and not enough to the process.



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  • It might be a plan (at least in a popular science magazine) to celebrate these self effacing acts at the end of each year and (just for fun) prioritise them by apparent bravery, (how much work compromised etc.).

    I like this idea. Call it the Integrity of Science medal with various classes. It would be a badge of high honour in the scientific community. Recognition by peers that you were prepared to do science the right way, instead of the religious way. Might make a very good secular media article as well. The comparison of this award with the religious.



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  • David R Allen Sep 6, 2014 at 6:28 pm

    I like this idea. Call it the Integrity of Science medal with various classes. It would be a badge of high honour in the scientific community. Recognition by peers that you were prepared to do science the right way, instead of the religious way. Might make a very good secular media article as well. The comparison of this award with the religious.

    I think it would be particularly praise-worthy, if having withdrawn a premature paper because of inadequate evidence, further research subsequently produced new conclusive evidence confirming the original hypothesis – perhaps with minor modifications!



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  • Sadly, this has every likelihood of not being possible. Further research funding may be compromised by such zealous honesty.

    Every pressure is needed to help those making funding decisions understand that zealous honesty may map less frequently to a positive result, but when it does so, the quality will be a notch or two higher.



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  • Hi Reckless.
    If ‘data fudging’ is rampant as the book suggests, a lot of reputable findings must still be getting through. The results of scientific endeavour speak for themselves. Look at the ‘cure rate’ of cancer, for instance. This is the case for most ailments,plus the increase in life-span and our ever lowering rate of infant mortality! Something is going right despite the occasional incidence of fraud. I’m not trying to justify dishonest practices by any means, but I hate to see science discredited by the odd failure in ethics.



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  • Hi Nitya,

    Agree, I’m sure some of it goes on, but as ultimately others scientists will come along and replicate work and get different results any errors or fraud will eventually be corrected. He comments on Gallielo for example and his miscalculations in relation to the orbits of the planets around the Sun as inaccurate. This may be true but as he had already done the conclusive experiment of viewing the changing shadows (phases) on Venus and Mercury there was only one physical explanation for this and that was that the Sun was in the centre of the solar system. I haven’t finished it, he is kind of celebrating scientists playing fast and loose to gain advantage and he might be right to a point but like you for me this is nothing to celebrate, I’m sure for every example he states there are others where such tactics have impeded science. I encountered one of these myself.

    I was at a conference for science teachers where all the teachers there had to present what they were doing, I was presenting some stuff I had been doing around astronomy with my year 8 class. So they have a scientist come to talk to us about her work in assisting healing with a treatment that took the 3D structure of proteins into account (I cannot remember the details now). I was enthralled as she described the the process she discovered as an undergraduate and then horrified as she boasted how rich she had become after the funding poured in after the patent and all the delays in actually getting the treatment to human trial (due to the process of protecting their intellectual property) now a decade latter and not a single patient treated and was only just published (after the patent was in place). Don’t get me wrong I don’t blame her personally, I’m happy for her to make a bundle of money. However by the end of the lecture it was abundantly clear that the system which is largely set up to protect intellectual property which came out of a university system which was in part at least subsidised by public funding. At the beginning of the talk she gave stats and to how many Australians die every year from untreatable ulcers, all I could do by the end was add up how many lives where being lost as her company delayed human trails or publish results until their financial self interest was secured.

    I personally would prefer to see more public funding and the science published as soon as discoveries are made available to all. The science eventually gets through in-spite of all this but this side of things disappoints me. Of course the only way of combating this is to have a general public prepared to fund pure research and see that the benefits will eventually flow on to all.



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  • . Reckless,….Agree, I’m sure some of it goes on, but as ultimately others scientists will come along and replicate work and get different results any errors or fraud will eventually be corrected

    It’s the correcting mechanism part of science that I love. Eventually an approximation of truth will come out, but even then it only stands for as long as it can go unchallenged. A great method!

    Your example of a scientist being able to report ‘raking it in’ after making a discovery was really surprising. I don’t think this happens very often. One of my family members lives from grant to grant as her job depends on her the ability of her superiors to secure a grant each year. I suspect this is the more usual state of affairs. To the best of my knowledge, she could only enter the realms of the highly paid by working for a large pharmaceutical company and I think this would involve marketing. There’s something weird about our value system but this is the way things work in the real world. Sad!



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  • Nitya,

    I agree, for me science is the cycle of discovery, test, refute, modify and so on which eventually leads to knowledge. The example I gave was I think rare too, I work with several scientists who have due to the poor public funding of science had to go into teaching (a win for teaching) because as you describe they were either working from grant to grant or their sector had funding cut year after year and downsized until they just didn’t exist any more.

    The organisers of the conference obviously chose her as an example of what the organisers considered a successful scientist. All I could think at the time was that it wasn’t a mark of success that I recognised. She was clearly a gifted scientist to have made the leap of intuition that lead to her discovery and instead of spending the next decade doing more of the same she spent it setting up a company, organising patents and preparing all involved to make money out of the enterprise. None of which she was trained for (so inefficient if nothing else) and opportunity to further her research lost in the quest to commercialise her discovery.

    The Wright Brothers who I admire greatly used data from Otto Lilienthal, and our own Lawrence Hargrave’s (and others) papers to understand the physics of flight these were freely published papers. They did make many independent discoveries (and Otto’s numbers were out – so they used a wind tunnel to derive the correct values) however, on solving the fundamental problem of heavier than air flight they desperately attempted to pursue their patients into court left right and centre and as a result their own progress was far outstripped by others. The saddest thing about them was this petty legalistic pursuit that IMO destroyed the competitive head start they had gained and turned them into bitter recluses. They had built on the knowledge of others who freely gave to the world.

    Until the world is willing to give a stable income to those who discover however the money driven incentive will dominate some of these fields, and progress will slow as a result. But yes most scientists I know are as you describe, underpaid, undervalued and vitally important.



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  • Hi Reckless.
    The most reliable way to earn a living as a scientist seems to be as a teacher. It’s possible to then rise through the ranks and gain promotions, but that’s an entirely different set of skills. As you said, they are generally underpaid and undervalued.



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