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Longevity Genetics Paper Finds New Home

01/19/2012
David Levine

After being retracted last year because of technical concerns, a study on the genetics of longevity has been re-analyzed and re-published.

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While environment and family history are factors in healthy aging, genetic variants play a critical and complex role in conferring exceptional longevity, according to a new paper published this week in PLoS One (1).

If this sounds familiar, it is. In 2010, led by Thomas Perls, associate professor of medicine at the Boston University School of Medicine, the same research team published a study with the same title online in Science (2). In that paper, the group reported on a genome-wide association study (GWAS) of exceptional longevity in 1055 centenarians and 1267 controls to determine how genes contribute to healthy aging. From this data, they built a genetic model of 150 single-nucleotide polymorphisms (SNPs) and reported that it could predict longevity with an accuracy of 77%.

After being retracted last year because of technical concerns, a study on the genetics of longevity has been re-analyzed and re-published.Source: Boston University School of Medicine, New England Centenarian Study







Almost immediately, outside researchers raised serious questions about the study. Specifically, they questioned the small sample size, the use of cases and controls drawn from different times and places, and the use of different technologies to analyze the DNA. Also, there was concern that the Illumina DNA chips used might have produced flawed data. As a result, the authors voluntarily retracted the paper in 2011, maintaining that their findings were supported by the data but would require new analysis that would constitute a new paper (3). Although there was no misconduct by the researchers, the editors of Science stated that the resubmitted data would not merit publication in the journal.

For their new paper, the authors hired researchers from Yale University to independently assess and help to produce a valid genotype data set for which the same analysis as in the original paper was performed. In addition, the team added an additional replication data set of subjects whose average age of 107.

“This new group was crucial to validating our initial findings,” said Perls. “As in our prior study, we found that those subjects who shared the same profile of variations for genetic markers in the model appeared to share similar levels of risk for various traits or diseases associated with exceptional longevity —most notably, in their ages of survival.”

In addition, the techniques used in the new study have both greater sensitivity and specificity. In their discussion, the authors noted that their new model predicted exceptional longevity with 60–85% accuracy, supporting their hypothesis that genes play an increasingly strong role in survival in centenarians.

“We built a genetic model that includes 281 single SNPs, discriminated between cases and controls of the discovery set with 89% sensitivity and specificity, and with 58% specificity and 60% sensitivity in an independent cohort of 341 controls and 253 genetically matched nonagenarians and centenarians,” said Perls.

Coinciding with the new study's release, the editors of the PLoS ONE Community Blog wrote: “The paper published today is the corrected and peer-reviewed version of their findings, with additional authors who independently validated the data and methodology, as well as an additional sample of centenarians used for replication purposes. As stated in the retraction notice, the primary findings remain the same, but the SNPs incorrectly identified in the original study have been removed from the model for predicting longevity.”

In an interview with journalist Ivan Oransky, executive editor of Reuters Health and author of the blog Retraction Watch, Perls was asked why the current paper does not cite the previous retracted paper. In response, Perlis wrote: “It frankly did not occur to me to do so (nor did any reviewer or editor suggest it). After all, it seems to me that it was Science’s intention to erase the paper we submitted to them from the scientific record as if it never existed so that we could publish it elsewhere…thus, what would be the purpose of citing the retraction?”

According to Oransky: “There’s no official obligation to cite a paper you’ve retracted. At the same time, we’d argue that it was precisely because the previous paper had issues that reviewers and readers would want to know about it. Showing a particular thread of research as it is, after all, consistent with the self-correcting nature of science.”

References

1. Sebastiani, P., N. Solovieff, A.T. DeWan, K.M. Walsh, A. Puca, et al. 2012. Genetic Signatures of Exceptional Longevity in Humans. PLoS ONE 7(1): e29848. doi:10.1371/journal.pone.0029848.

2. Sebastiani, P., N. Solovieff, A. Puca, S.W. Hartley, E. Melista, et al. 2010. Genetic Signatures of Exceptional Longevity in Humans. Science 10.1126/science.1190532

3. Sebastiani, P., N. Solovieff, A. Puca, S.W. Hartley, E. Melista, et al. 2011. Retraction. Science 333: 404.