Genetic Future

More on return of research data to participants from Genomics Law Report

Wed, 04 Nov 2009 13:15:00 -0500

Yesterday I posted a brief rant about the need for researchers to think about the best way to return genetic research data to participants, spinning off an equally brief opinion piece I wrote for the ongoing ELSI series at Genomics Law Report.

Today Dan Vorhaus has posted an excellent piece on the same topic over at GLR, triggered by an exchange between 23andMe's Anne Wojcicki and Kaiser Permanente. Go check it out.

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Research subjects should have access to their own data

Tue, 03 Nov 2009 10:15:00 -0500

My contribution to Genomics Law Report's superb "What ELSI is New" series is up now.

The gist of my argument: as we move into an era of large-scale whole-genome sequencing studies and the utility of genomic information grows, researchers will increasingly frequently be faced with the discovery of highly medically relevant information within their subjects' genomes. Yet under the consent procedures established for most modern genetic research projects the anonymised subjects would never have a chance to learn about this information.

As such, people will die from breast cancer and other diseases even though someone out there possesses genetic information ~~they would have needed to avoid this~~ that could have been used to guide additional screening to detect such cancers early.

Throwing medically actionable data away without the subjects ever having a chance to learn about it is unconscionable - we need to start changing the way we think about the rights of research subjects to their own data.

It's important not to understate the challenges posed by returning research data to research subjects - such as balancing against the need for privacy and data security, or unduly alarming people with inaccurate results - but these are not reasons to avoid data return. They are simply obstacles we need to overcome.

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First ever association study using whole genome sequences

Tue, 03 Nov 2009 07:30:00 -0500

New-technology DNA sequencing provider Complete Genomics will provide near-complete genome sequences of 100 individuals to the Institute for Systems Biology, driving the first ever association study for a complex trait using whole-genome sequencing. Here's the press release, and GenomeWeb has some additional information.

This is pretty exciting stuff:

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What happens when a DTC genomics company goes bust? Follow up post on Genomics Law Report

Tue, 27 Oct 2009 12:00:00 -0500

A while back Dan Vorhaus and Lawrence Moore wrote a fantastic series of guest posts here on Genetic Future on the issue of what would happen to customer data in the event that a direct-to-consumer genetic testing company went bankrupt - here's the introduction, a detailed analysis of the implications of bankruptcy law, and a summary of the implications for consumers.

Lawrence Moore and Emily Sherlock now have a follow-up post over at Genomics Law Report digging into the implications of federal privacy regulations in the event of a DTC genomics company collapse.

The rather worrying conclusion is that "at present it does not appear that there is any federal regulation--including HIPAA--that clearly restricts the transfer of customers' information as part of a sale of assets by a troubled DTC genomics company." Given that uncertainty, Moore and Sherlock conclude:

...the most practical advice at this time, for existing and potential customers, continues to be to understand the terms and conditions offered by each individual DTC genomics company with respect to their customers' information--and to recognize that, in bankruptcy, genomic data may be transferred to a similar company without regard to those terms and conditions.

There's also a tantalising promise of posts to come in the near future exploring the implications if impending regulatory changes in the DTC genomics area push testing companies firmly into the realm of clinical diagnostics.

Genomics Law Report continues to impress with the quality and diversity of its posts - if you haven't already added it to your RSS reader (and added @genomicslawyer to your Twitter feed) you should go and do so without delay.

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23andMe presents novel genetic associations at American Society of Human Genetics meeting

Sun, 25 Oct 2009 05:30:26 -0500

It's been an intensive week of genomics here at the American Society of Human Genetics meeting, and I haven't been able to grab time to blog as much as I'd have liked. In fact there's a whole load of genomics news I'll be trying to cover in some detail over the next couple of weeks; for the moment, though, I couldn't let today's presentation from personal genomics company 23andMe go by without at least some comment. (For other coverage of the conference, do check out Luke Jostins' blog coverage and the stream of live analysis on Twitter.)

The 23andMe presenter (Nick Eriksson) delivered an overview of the potential of the 23andMe cohort for association studies: all 23andMe customers have genetic information for over 500,000 common genetic variants, and they are also encouraged to provide self-reported phenotype data on a wide range of traits ranging from the presence of detached earlobes to longitudinal tracking of Parkinson's disease symptoms. Eriksson reported that the company now had sufficient numbers of returned surveys to perform genome-wide association studies for 22 traits, with sample sizes ranging between 2500 and 6000 individuals - reasonable sample sizes for an initial look at the genetic architecture of a complex trait.

The company seems to be doing a reasonable job of identifying and controlling for the various potential confounders that plague genome-wide association studies, such as population structure. However, 23andMe faces an unusual challenge that standard academic GWAS consortia don't: the possibility that a subject will give a biased trait report after seeing their own genetic data.

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Off to Hawaii... and looking forward to new associations from 23andMe

Wed, 14 Oct 2009 19:15:00 -0500

I'll be away for the American Society of Human Genetics meeting in Hawaii for most of the next couple of weeks - I'll be covering the conference primarily via Twitter, and you can follow all of the tweets from the conference using the #ASHG2009 hashtag.

Genetics bloggers/tweeters should also pencil in the "tweetup" on Thursday 22nd from 4:30 to 5:15 in the ASHG Press Office (Room 318 in the Convention Center), organised by Chris Gunter; anyone interested should RSVP via email. This should be a good chance to put faces to many of the names in your Twitter and RSS feeds.

There's a lot of talks I'm looking forward to, but here's one of particular interest to those who follow the personal genomics industry (and a useful counterpoint to my critique of 23andMe's NFL genetics press release yesterday):

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23andMe performs genome-wide association study on NFL players, fails to find athlete genes

Tue, 13 Oct 2009 12:30:00 -0500

Details are pretty sketchy, but a press release announced today suggests that personal genomics company 23andMe has performed a genome-wide association study comparing 100 current or former professional NFL players with a set of controls of unspecified sample size.

The shocking result:

The study did not find the tested players to be genetic outliers, suggesting that genetics may not be a good predictor of athletic success.

It's unsurprising that the results of this study are negative (more on this below), but the conclusions they draw from this are fallacious. In fact we know from twin and family studies that many (but not all) traits related to athletic performance are highly heritable; researchers just haven't been able to track down the vast majority of the genetic variants responsible yet, and this study is no exception.

What 23andMe have actually shown here is that the limited subset of genetic variation captured by their genotyping chip (which almost exclusively targets genetic variants with a frequency of greater than 5%) doesn't include any variants with an extremely strong association with NFL prowess.

That shouldn't come as a surprise to anyone who's been following advances in human genetics for the last few years; a genome-wide association study on a highly complex trait with a sample size of 100 has, historically speaking, a vanishingly small chance of yielding any positive results at all. (Yes, there are exceptions, but I don't think a sensible prior expectation would be that athletic performance has a similar genetic architecture to macular degeneration.)

The press release argues that the results "speak to the breadth of the genetic research the company is undertaking". That may be so, but I certainly hope they aren't indicative of the general quality of 23andMe's research program. Much as I hate to say it about a company whose work I generally admire, this study carries all the hallmarks of being pure PR fluff. If you want to do a GWAS for athletic performance, at least wait until you have a homogeneous sample that's well-powered enough to have a fighting chance of detecting real associations.

On the bright side, 23andMe has been building up much more sensible sample sizes for other projects, including 4,500 older amateur athletes and over 3,000 Parkinson's disease patients. I'm hopeful that we'll see something a little more interesting than this NFL story roll out of the company over the next few months.

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Scientists call for changes to personal genomics based on comparison of test results

Wed, 07 Oct 2009 21:20:00 -0500

Four scientists - including the omnipresent J. Craig Venter (left) - have penned an opinion piece in the latest issue of Nature based results from five individuals genotyped by two separate personal genomics companies. The article highlights some deficiencies in the way that genetic data are currently used by direct-to-consumer companies to generate risk predictions and to present them to customers.

The identity of the tested individuals isn't made explicit in the article, except to note that there were two males and two females from the same family and one unrelated female. All of the individuals were tested by the companies 23andMe and Navigenics, which examine ~580,000 and ~923,000 sites of common genetic variation (SNPs), respectively. It's worth noting that in both cases the scans were performed before the companies were required to comply with CLIA standards (meaning that genotyping accuracy may have improved somewhat since these scans were done).

The first result is reassuring: the concordance between the genotype calls from the companies was excellent, with disagreements at fewer than one in every 3,000 sites. Previous comparisons (see comments on this article) between 23andMe and deCODEme have found even smaller discrepancy rates, closer to one error in every 25,000 sites - the difference appears to be due to a substantially higher error rate on the Navigenics platform compared to 23andMe (compared to research-quality typing performed on the same samples, Navigenics had a 0.29% discordance compared to 0.01% for 23andMe). Overall, though, it's clear that the levels of technical accuracy being achieved by the genotyping platforms used by major personal genomics companies are perfectly acceptable.

The real challenge is not with generating the raw genetic data, but rather with converting it into disease risk predictions - and here, the authors argue, the results of the comparison are less than ideal:

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Nature special issue a treasure trove for personal genomics fans

Wed, 07 Oct 2009 18:30:00 -0500

The latest issue of Nature contains an embarrassment of riches for those of us interested in personal genomics, and indeed I'm having trouble figuring out which article to write about first.

Just look at the options: there's a review on approaches to tracking down the missing heritability of common diseases; there's a potentially highly controversial plea from Chicago researcher Bruce Lahn for acknowledgment that "genetic diversity contributes to variation across numerous physical, physiological and cognitive domains" between human populations; and there's an advance online publication describing the highest-resolution survey yet performed of large-scale structural variation in the human genome (on which I am proud to be fifteenth author!), accompanied by a tidy News and Views piece from John Armour.

Any of these would provide ample fodder for a post, but right now I only have time to write about one. Hmmm...

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IBM's foray into nanopore sequencing: are they serious contenders?

Tue, 06 Oct 2009 11:00:00 -0500

IBM's announcement that it will be entering the DNA sequencing technology race (which I mentioned briefly earlier today) has created a tremendous amount of mainstream media interest. That's understandable given IBM's size and history of innovation, but how likely are they to represent serious contenders for the potentially lucrative sequencing market?

Firstly, it's important to note that this announcement represents more of an expression of interest in the field rather than anything close to a mature technology; IBM will not be rolling out a machine to sequence your genome at any stage in the near future. Rather, the press release seems to have been triggered by yesterday's announcement that IBM had been awarded a $557,000 grant from the National Human Genome Research Institute to help develop the sequencing technology.

IBM's proposed technology (which would make use of solid state nanopores, basically tiny holes in a silicon membrane) would certainly offer substantial advantages over existing sequencing platforms, but there remain some serious challenges to developing this tech. A friend working in the nanopore area proposed these as the most serious obstacles ahead:

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News in genomics

Tue, 06 Oct 2009 06:30:00 -0500

Things are as usual moving at ludicrous speed in the world of genomics, but sadly I only have time to post a few pointers to some of the most striking developments.

IBM is moving into the third-generation sequencing arena. The company is developing a new sequencing technology based on tiny nanopores - a field already being explored by the understated British nobility of sequencing, Oxford Nanopore. This is all over the news, but Dan Vorhaus has an introduction and is promising to follow up on further developments. You can also watch a pretty but largely content-free animation of the process.

Speaking of Dan Vorhaus: the superb blog Genomics Law Report has just launched a new series, What ELSI is New, consisting of brief guest posts from a diverse range of authors on emerging ethical, legal and social issues in genomics. Already there have been two instalments posted, one from Hank Greely and another from Misha Angrist - both well worth a read. I have also committed to writing my own contribution (it's on its way, Dan!).

Finally, a new program at Beth Israel Deaconess Medical Center will push medical students trainee pathologists towards a better understanding of new genetic tests:

Doctors in their second and final years of pathology residency training will take the class - attending lectures and researching the science behind the tests. If they choose, they can look at their own test results, submitting a sample to the genetic testing company Navigenics.

Given that 23andMe now dominates the genome scan market (meaning it will be the company most prospective patients will be using), and that the company plans to offer discounted tests to doctors, Navigenics seems like a strange choice.

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UK backing away from controversial refugee tests?

Tue, 06 Oct 2009 06:00:00 -0500

Last week I noted a highly controversial plan by the UK Border Agency to begin using DNA and isotope testing to help determine the geographical origins of refugees, for use in making decisions about whether or not to grant asylum.

A reader has just pointed me to this recent post on ScienceInsider indicating an apparent change in policy: the Border Agency has now stated that the trial will be "proof of concept" only, and that "no decisions on individual cases will be made using these techniques, and they will not be used for evidential purposes". As ScienceInsider notes, this represents a pretty clear shift in language compared to earlier announcements.

Some of the furore around this policy was overstated (I agree with Razib's comment that uncertain information can still be quite useful in the context of Bayesian assessments of the accuracy of an asylum seeker's tale of woe), but the initial policy was still grossly premature. I welcome the Border Agency's decision to take a step back and consider the implications before wading into the morass of genetic ancestry testing.

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Outrage over DNA testing for UK asylum seekers

Tue, 29 Sep 2009 08:00:00 -0500

ScienceInsider reports that plans by the UK Border Agency to employ DNA and isotope testing to test the origins of asylum seekers are being met with outrage by scientists and refugee advocates.

There's not much information about the precise tests that will be employed, but what information has been made available has horrified a number of scientists including the University of Leicester's Alec Jeffreys:

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Guest post: what happens when a personal genomics company goes bankrupt (part 3)

Wed, 16 Sep 2009 09:00:00 -0500

In this final post of their three-part series, lawyers Daniel Vorhaus and Lawrence Moore of the superb blog Genomics Law Report analyse the legal repercussions of a personal genomics company going bankrupt. In part one of the series Vorhaus and Moore analysed the privacy policies of two representative personal genomics companies, while part two was a detailed examination of the complex legal issues surrounding the treatment of customer genetic data in the event of company bankruptcy.

In this final installment, Vorhaus and Moore bring it all together to explain the implications for personal genomics consumers.

Part III: What Does It All Mean?

In part one, we discussed the importance of Privacy Policies and other legal agreements in determining how DTC genomics companies will treat their customers' information, including in the case of a bankruptcy sale. Unfortunately, but not surprisingly, we failed to find much in the way of concrete answers. In part two, we dug into the law to investigate how a bankruptcy court would be likely to evaluate the proposed sale of a company's genomic database, including in what scenarios it might be willing to set aside the company's own agreed upon Privacy Policies. In this final part, the threads come together as we ask--and attempt to answer--the only question that really matters for most readers: what does it all mean for the average DTC genomics customer?

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The informatics of new sequencing technologies

Wed, 16 Sep 2009 07:00:00 -0500

Kevin Davies from Bio-IT World has two interviews up today relevant to new DNA sequencing technologies.

Firstly, there's an excellent interview with Clive Brown, vice president of development and informatics for Oxford Nanopore Technologies - one of the most promising contenders in the rapidly evolving third-generation DNA sequencing market. Brown is renowned for his plain-speaking approach (in the article he's described as "the most honest guy in all of next-gen sequencing", a quote originating from David Dooling), and that shows here in his blunt comments on the recent Helicos genome publication (covered here), the technical and marketing challenges faced by new seq tech companies, and the process of poaching employees from the Sanger Institute.

Secondly, Kevin Davies interviews David Dooling, who heads informatics at The Genome Center at Washington University at St Louis (and also writes an excellent blog, PolITiGenomics). Dooling explains why Wash U. chose to invest in the Illumina platform rather than SOLiD, advocates the use of open source software for large-scale genomics, and discusses the transition to third-generation technologies looming on the horizon.

Meanwhile, for those fortunate enough to have subscriptions, GenomeWeb has a dense crop of interesting articles just out including an intriguing investigation into the real costs of sequencing a human genome. The article notes a surprisingly wide range of cost estimates even for providers employing the same technology (Illumina), especially once frequently under-appreciated costs such as detailed downstream informatic analysis are factored in.

Thus, while Illumina is now offering genome sequences at a retail price of $48,000, Stephen Kingsmore, president and CEO of the National Center for Genome Resources, argues that the true cost of a very high-quality finished sequence is closer to $250,000. Kingsmore argues that a large chunk of this cost comes from the current need for intensive manual analysis of the resulting sequence, a cost that will decline precipitously as sequencing technology and informatics solutions improve.

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