When a group of researchers last year claimed to have found a “genetic signature” to identify people likely to live to 100, they were questioned immediately. Now they’ve retracted the controversial paper — but continue to stand behind their assertion.
After online publication of our report “Genetic Signatures of Exceptional Longevity in Humans” (1) we discovered that technical errors in the Illumina 610 array and an inadequate quality control protocol introduced false positive single nucleotide polymorphisms (SNPs) in our findings. An independent laboratory subsequently performed stringent quality control measures, ambiguous SNPs were then removed, and resultant genotype data were validated using an independent platform. We then reanalyzed the reduced data set using the same methodology as in the published paper. We feel the main scientific findings remain supported by the available data: (i) A model consisting of multiple specific SNPs accurately differentiates between centenarians and controls; (ii) genetic profiles cluster into specific signatures; and (iii) signatures are associated with ages of onset of specific age-related diseases and subjects with the oldest ages. However, the specific details of the new analysis change substantially from those originally published online to the point of becoming a new report. Therefore, we retract the original manuscript and will pursue alternative publication of the new findings.
The notice is signed by all of the authors, beginning with lead author Paola Sebastiani. The reasons for the retraction are clear, and the notice seem to respond quite well to concerns raised by Science and others. The retraction, Science takes pains to note in an accompanying statement, had nothing to do with fraud:
Science emphasizes that there was no misconduct by Sebastiani and colleagues. The researchers worked exhaustively to correct the errors in the original paper and we regret that the outcome of the extensive revision and re-review process was not more favorable.
David Goldstein, a genetics researcher at Duke who had suggested what was wrong with the paper in a smart piece by Newsweek’s Mary Carmichael last year, told Retraction Watch:
This seems to settle it and I think the authors are doing the right thing in explaining the artifact in the retraction.
We agree. Being the fine-toothed comb retraction notice readers we are, however, we were curious about this line:
We feel the main scientific findings remain supported by the available data
It reminded us of the Bulfone-Paus saga, in which journals allowed four of the group’s retraction notices to claim that the data and conclusions had been confirmed, without an editor reviewing said data. So we asked Sebastiani for details on the new findings, and whether they had submitted them anywhere yet. Through a spokesperson, Sebastiani and co-author Thomas Perls said:
We will be happy to discuss our amended findings as soon as they are published.
But this was in fact different from the Bulfone-Paus case, not only because that episode involved misconduct and this one didn’t. Science took a hard look at the new Sebastiani et al data, using peer review, and found it wanting. In a statement, the journal explains why the findings — if they make it through peer review, of course — will be published somewhere other than Science.
Sebastiani and colleagues submitted the corrected data to Science in December 2010, where the work underwent careful peer-review. Although the authors remain confident about their findings, Science has concluded on the basis of peer-review that a paper built on the corrected data would not meet the journal’s standards for genome-wide association studies. One such standard, for example, is the inclusion of a reliable replication sample that shows comparable results to those in the initial experiments.
The authors have therefore agreed to retract their paper.
We’ll keep an eye out for a new paper describing the results.
Watch Sebastiani and Perls discuss their findings in a BU video released a week after the study.