Scientist Smackdown: Experts Question Study of Longevity Genetics

By Joseph Calamia | July 8, 2010 12:11 pm

genechipWe can predict your chances of living exceptionally long, with 77 percent accuracy, by looking at 150 tiny genetic variants. That’s what researchers claimed in a Science paper that we described last week. Those predictive powers have left some feeling a little uneasy–and not just about what futures are buried in their genomes. Where the paper‘s authors saw correlations, some experts are now seeing errors from DNA testing chips.

No DNA chip is perfect; it can get things wrong as it sorts through hundreds of thousands of genetic variants. In fact, certain chips might even make the same error repeatedly. That could cause problems, because what looks like a genetic variant common to a group of people could instead just be an echoed flaw in one chip’s testing capabilities.

Newsweek, which broke this story, reports that the Boston University researchers who led the study did, in fact, use different chips, but not enough different chips to rule out this potential error. They used two different types of DNA chips to test the centenarian group (about 1,000 people whose ages ranged from 95 to 119): a 370 chip that examines 370,000 genetic variants and a 610-Quad that examines 610,000 variants. The control group (of about 1,200 younger people) was tested with those two chips and a few others, thus possibly hiding any shared errors.

David Goldstein, the Duke University geneticist who first questioned this method at Newsweek last week, says that using similar chips (both made by Illumina) for the centenarian group and a collection of different ones for the control group could have left the researchers wide open for errors.

“Unfortunately, different chips have their own little problems for specific [genetic variants],” he says. The key to keeping false positives at bay is to ensure that cases and control groups are analyzed using exactly the same techniques. If you use one type of chip to analyze your cases and a different type to analyze your control group, “you can see any [variants] that are genotyped differently on the different chips ‘lighting up’ as apparently associated with the trait,” says Goldstein, when in fact that pattern is just an experimental artifact. [Newsweek]

DISCOVER’s Razib Khan has also posted in Gene Expression on various hints that this study might not be all that it’s cracked up to be. Khan takes note of skeptical claims from other experts and the commercial testing company 23andMe, which, after the study’s fanfare, tried to see the relationship between these tiny variants (called SNPs) highlighted by the study and their older clients’ genomes.

We took a preliminary look in our customer data to see if the proposed SNP-based model described in Sebastiani et al. is predictive of exceptional longevity. . . . [B]ased on our data, performance of this model is not significantly better than random. [23andMe]

The study’s authors led by Paola Sebastiani and Thomas Perls released a statement yesterday apparently in response to the Newsweek article and comments from Kari Stefansson, the leader of a similar study quoted in the New York Times. The Boston University researchers are checking their results.

“We have been made aware that there is a technical error in the lab test used on approximately 10% of the centenarian sample that involved the two of the 150 variants. Our preliminary analysis of this issue suggests that the apparent error would not effect the overall accuracy of the model. Because the issue has been raised since the publication of the paper, we are now closely re-examining the analysis. Another question that was raised concerns the criteria used to determine if an association between a genetic variant and exceptional longevity was statistically significant. We used standard criteria for the analysis, and we are confident that the appropriate threshold was used.” [Newsweek]

Related content:
Gene Expression: The short life expectancy of longevity genes (?)
80beats: What Can Centenarians’ Genes Tell Us About Getting Old?
Not Exactly Rocket Science: Genetic signatures for extreme old age accurately predict odds of living past 100
80beats: A Life-Extending Coup: Flies That Can’t Smell Food Live 30 Percent Longer
80beats: Low-Calorie Diet Staves off Aging & Death in Monkeys
80beats: Immunosuppressant Drug Extends Lifespan of Elderly Mice

Image: Wikimedia / Schutz

CATEGORIZED UNDER: Health & Medicine
  • clipart

    For what it’s worth, your story is accompanied by a photo of an Affymetrix chip instead one made by Illumina.

  • http://www.earthlab.net Brandon Keim

    The study didn’t say “We can predict your chances of living exceptionally long, with 77 percent accuracy, by looking at 150 tiny genetic variants.” It said, “By looking at 150 genetic variants, we can tell, with 77 percent accuracy, whether or not you’ve already lived very long.”

    That’s a key difference. If you live to 100, there’s a 77 percent chance you’ll have the genes; but if you’re in middle age and have the genes, the chance you’ll live to 100 is still miniscule — just less miniscule than everyone else.

  • Joseph Calamia

    Brandon,

    Sorry for the delay responding–didn’t see your comment. Thanks very much for it—and for checking out my post. A quote from your Wired story gets to the heart of it, and I wish I had come across it earlier:

    “The researchers used these results to develop statistical models of longevity-associated gene profiles. Used to evaluate anonymized sample genomes, the model could predict whether the sample came from a centenarian with 77 percent accuracy, underscoring the importance of genetics in extreme long life.”
    [http://www.wired.com/wiredscience/2010/07/centenarian-genetics/#more-23349]

    That seems a very clear description of their procedure and doesn’t make any other claims about what “predict” means.

    Perhaps that’s the problem–the word, “predict.” It seems to indicate that scientists can tell beforehand who will live to be 100 years old. I noticed in your comment above that you avoided using the word altogether in your rephrasing of my lede, perhaps to avoid just this confusion.

    It’s unfortunate that the researchers used the word in their abstract. I would guess they meant it in the way you describe: predict, before looking at the samples’ identification, which ones came from centenarians, but it is confusing in both the abstract and Science press release.

    From the abstract:
    “Using these data, we built a genetic model that includes 150 single-nucleotide polymorphisms (SNPs) and found that it could predict EL [exceptional longevity] with 77% accuracy in an independent set of centenarians and controls.”

    Perhaps this caused many reporters to write that the scientists had found a test that could tell whether people would live a long life:

    “Researchers have found a pattern of genes that predicts with more accuracy than ever before who might live to be 100 or older — even if they have other genes linked with disease.”[Reuters]

    “If you were going to live to be 100, would you want to know it? When it becomes affordable to have one’s genome sequenced, perhaps in a few years, a longevity test, though not a foolproof one, may be feasible, if a new claim holds up. Scientists studying the genomes of centenarians in New England say they have identified a set of genetic variants that predicts extreme longevity with 77 percent accuracy.”[NYTimes]

    “A genetic test that can predict whether a person is likely to live long enough to see their 100th birthday has been developed by scientists…Researchers at Boston University claim the test can identify those who can look forward to an exceptionally long life with 77% accuracy.”[guardian.co.uk]

    Again, I wish I had read your piece before posting.

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