Genetic Future

Guest post: Neil Walker on the curious case of the schizophrenia GWAS

Fri, 17 Jul 2009 08:00:00 -0500

Purcell et al. (2009). Common polygenic variation contributes to risk of schizophrenia and bipolar disorder Nature DOI: 10.1038/nature08185

Neil Walker has been doing a spectacular job of serving up useful information in the comments recently, so I asked him to write the first ever guest post on Genetic Future - something that (as I will be announcing shortly) I intend to do fairly regularly over the next couple of months.

The topic is a paper that has created a rather perplexed buzz recently in the complex disease genetics community: the genome-wide association study (GWAS) for schizophrenia published in Nature last week. This paper takes a novel and (at first glance) rather alarming approach to exploring the genetic basis of this complex disease, so I asked Neil to provide some insight into what he thought about the approach used in this paper and what it means for complex disease genetics.

Without further comment, I present Neil's post:

Read the rest of this post... | Read the comments on this post...

New blog to follow: Genomics Law Report

Thu, 09 Jul 2009 18:50:40 -0500

A quick pointer to a new blog on the genomics scene that's just been officially launched: Genomics Law Report, a corporate blog from legal firm Robinson, Bradshaw and Hinson. One of the contributors, Dan Vorhaus, is an advisor to the Personal Genome Project and provides one of the highest signal-to-noise ratio genomics feeds on Twitter.

Dan's latest post, an excellent analysis of 23andMe's latest push into consumer-driven research, is a good place to start reading.

Subscribe to Genetic Future.

Follow me on Twitter.

Read the comments on this post...

Call for submissions to Nuffield Council on Bioethics inquiry into personalised medicine

Wed, 08 Jul 2009 08:52:34 -0500

I just received the following email from the Nuffield Council on Bioethics - I'd recommend anyone interested in the future of personalised medicine in the UK consider submitting their views to the inquiry. I'll be putting together my own submission, which I'll also post here on Genetic Future.

Medical profiling and online medicine: the ethics of 'personalised' healthcare in a consumer age

The Nuffield Council on Bioethics is currently running a consultation on Medical profiling and online medicine: the ethics of 'personalised' healthcare in a consumer age. The paper provides background information and asks questions on a number of different issues relating to medical profiling and online medicine. We are also inviting respondents to inform us about any other areas that we should consider. We are seeking the views of people including those who have used medical profiling and online medicine services, people working in the area and other stakeholders, academics, policy makers and members of the public. To this end, we would greatly value your contribution given your interest and expertise in genetics generally and personal genomics specifically.

We should be most grateful if you would also include a notice about this consultation on your website, to inform your readers that we are seeking their views. All documents can be downloaded from the Council's website or obtained by contacting us.

The role of the Council is to examine ethical issues raised by new developments in biological and medical research. It is an independent body, funded jointly by the Nuffield Foundation, the Medical Research Council and the Wellcome Trust. It works by considering topics in depth, publishing reports on its findings and making recommendations to policy makers.

In September 2008, the Council set up a Working Party to examine the ethical issues raised by medical profiling and online medicine, chaired by Christopher Hood, Gladstone Professor of Government at the University of Oxford. Further details about the Working Party, which also includes members with expertise in economics, genetics, law, medicine, philosophy, social science and telemedicine, can be found on the Council's website.

In its work, the Working Party will consider the ramifications of different technologies, including:

electronic health records;
web enabled health information;
internet based drug purchasing;
telemedicine;
body imaging; and
DNA profiling.

The deadline for responses is 31st July 2009. The Working Party will consider all the consultation responses received and use them to inform its deliberations. A report with conclusions and recommendations is expected to be published in Spring 2010, and a copy of the final report will be sent to all consultation respondents.

Read the comments on this post...

23andMe launches new effort to recruit patients for disease gene studies

Tue, 07 Jul 2009 20:00:00 -0500

Personal genomics company 23andMe has always differentiated itself from its more sober competitors through an emphasis on collaborative, consumer-driven research - essentially, encouraging its customers to contribute their genetic and trait data to internal research projects designed to find new genetic associations. It is widely believed that generating novel associations between genetic variants and traits is actually the core business strategy for the company, although the precise mechanism for converting such associations into cash-flow remains unclear.

The company's initial attempt at obtaining detailed trait information was via a system of online surveys for customers designed to harvest information about traits ranging from left-handedness to dental health, cutely titled 23andWe. The major problem with this type of approach is that most typical personal genomics customers don't actually carry the types of juicy phenotypes most attractive for association studies (i.e. common diseases and disease-associated traits), a deficiency the company has since tried to overcome through targeted recruitment of specific groups of people for much larger association studies (thus far restricted to Parkinson's patients and pregnant women).

Today 23andMe launched a new initiative, the somewhat less cutely-titled Research Revolution, that seeks to cast the net much more widely in recruiting customers with specific diseases. The initiative was not widely publicised, but it warrants close attention - both for what it tells us about 23andMe's overall business strategy, and the lessons it might have for academic groups seeking to recruit patients for large-scale genetic studies.

Read the rest of this post... | Read the comments on this post...

UK House of Lords report on genomic medicine: implications for DTC genetic testing

Tue, 07 Jul 2009 17:45:00 -0500

The UK House of Lords Science and Technology Committee has published the long-awaited report (PDF) from its inquiry into genomic medicine.

Mark Henderson at The Times has been busy today, putting out three excellent pieces on the report: a summary of the major implications, an opinion piece pushing the need for the health service to respond quickly to the arrival of genomic medicine, and a lengthy blog post praising the report and providing his views in more detail.

I find little to disagree with in Henderson's coverage, and certainly agree with his overall opinion of the report: this report is a careful, balanced analysis of the major issues facing health systems as they move into the era of genomic medicine. Since most of the problems the UK is facing in coping with this transition will also be issues for other developed countries, governments and health agencies around the world would be well-served by printing out a copy of this report and taking its major messages seriously.

I'd recommend reading all three of Henderson's pieces for the broader context of the report (and particularly for the implications for health services). Here I want to focus on the report's implications for the area closest to my interests: the direct-to-consumer genetic testing industry.

Read the rest of this post... | Read the comments on this post...

Conference blogging: icons for presenters

Mon, 06 Jul 2009 09:00:00 -0500

A while back I pondered the possibility of creating icons for conference presenters to add to their first slide to alert bloggers/tweeters in the audience about whether the presented data was "blog-safe". This was provoked by a recent episode illustrating general confusion among bloggers (in this case, me) and scientists about the use of social media at conferences.

Fellow Australian-turned-UK-resident-scientist Cameron Neylon has now put together a handy set of slides for presenters to label both "blog-safe" and "no-blogging" presentations. The slides have a ccZero license and so are freely available for download and modification; the original icons can be found on Cameron's Flickr account and Christopher Ross' website.

I think these slides are a great start, and I'd encourage anyone interested in the interface between science and social media to consider modifying them for their own presentations. I'd see the slides as being useful in a variety of situations:

Read the rest of this post... | Read the comments on this post...

23andMe leading push for regulatory changes for direct-to-consumer genetic testing

Wed, 24 Jun 2009 20:35:37 -0500

Pharmacogenetics Reporter has a lengthy article (subscription required) on the California bill SB 482, sponsored by personal genomics company 23andMe, which seeks "to distinguish so-called "post-CLIA bioinformatics services" from entities providing laboratory services".

In other words, 23andMe is pushing to have companies purely providing analysis of genetic data regulated separately from those doing the actual laboratory testing. Since 23andMe out-sources its testing to an external laboratory, this would exempt the company from some regulatory requirements. The move follows some fairly serious regulatory controversy over direct-to-consumer testing in California a year ago.

However, this isn't simply an attempt to make the situation easier for direct-to-consumer genetic testing companies. The bill also proposes regulations that would raise the bar for genetic testing companies, and hopefully close out some of the shadier operators in the space:

Read the rest of this post... | Read the comments on this post...

Genetic Alliance calls for a genetic test registry

Wed, 24 Jun 2009 19:10:02 -0500

GenomeWeb reports that the advocacy group Genetic Alliance is lobbying the FDA for the construction of a public registry of genetic tests:

[Genetic Alliance Director of Genetics and Health Policy Kristi] Zonno said FDA should create a public registry for genetic tests to "enable transparency and promote informed decision making for consumers and providers." She said that registry "could and should include the myriad of genetic, genomic, and pharmacogenomic testing available to the US market."

Open to the public, the registry should at the very least include the name of the lab performing a test, the name of the test developer, and information to support the test's usefulness in obtaining results and improving clinical care, Zonno added.

This move is long overdue - there have been discussions of the need for such a database in many circles for well over a year, but there has been no visible progress yet. This is an enormously complex industry, and consumers need guidance from independent bodies (certainly more than they need over-zealous regulation of the industry). If Genetic Alliance can convince FDA to make a real effort here that would be a major step in the right direction.

Subscribe to Genetic Future.

Follow me on Twitter.

Read the comments on this post...

Nature News article on conference blogging

Wed, 24 Jun 2009 18:01:04 -0500

Geoff Brumfiel has done a great job in this article for Nature News on the promise and perils of conference blogging. On the promise side there is discussion of the wildly successful FriendFeed coverage of last year's ISMB meeting, which ended up being aggregated into a journal article; in the perilous direction, I get a mention for my mildly disastrous foray into conference blogging at the recent Cold Spring Harbor Biology of Genomes meeting.

Brumfiel does a good job of conveying the currently chaotic state of conference policies towards the use of social media by participants:

Read the rest of this post... | Read the comments on this post...

The world's most annotated man

Tue, 23 Jun 2009 08:15:00 -0500

Update: In the comments below, SNPedia co-founder Michael Cariaso notes that Duncan has already lost his crown to the anonymous European NA07022, recently sequenced by Complete Genomics, who weighs in with 5891 associations to Duncan's 5321. Records don't last long in the age of high-throughput genomics!

Author David Ewing Duncan now officially has the most annotated genome of any human being; but given that the majority of those annotations are wrong and most of the remainder only weakly predictive, he's also a powerful illustration of how far we still have to go before the era of personal genomics comes to fruition.

Duncan isn't the person with the largest portion of his genome sequenced (Craig Venter, Jim Watson and Seong-Jin Kim are the named individuals currently competing for that honour), but he has so far cast his net the most widely in examining the potential functional information within his DNA. His 5,321 current associations come courtesy of SNPedia, a public database of genetic associations maintained by Michael Cariaso.

The majority of those associations, unfortunately, are pure noise - the detritus left behind by the noxious wave of false positives that was the era of the candidate gene association study, prior to the advent of modern, robust genome-wide association studies. Of the relative minority that are likely to be genuine, most are common variants with very small effects on disease risk and thus extremely limited predictive value. Wading through the sheer mass of loosely annotated data in Duncan's SNPedia report provides sharp insight into the challenges of navigating large-scale genetic data.

(Added in edit: In hindsight the paragraph above could be read as a criticism of SNPedia, which it isn't - SNPedia simply provides a catalogue of the genetic associations in the literature along with links to the relevant papers, and it's up to the user to decide what standards of evidence to apply in deciding whether or not an association is useful. So just to be clear - the emotive language in the paragraph is aimed towards the appallingly high levels of false positives in published genetic association studies and not towards SNPedia's decision to list them.)

It's clear that consumers will need tremendous guidance in that navigation - but it's still unclear exactly who will be the best at providing that guidance. The medical establishment certainly wants you to think that they are the only qualified providers, but upstart private personal genomics companies like 23andMe are giving clinicians a run for their money, and crowd-sourced efforts such as SNPedia remain a wild card.

In the meantime, Duncan isn't resting on his laurels - he says he plans to have his entire genome sequenced "soon" as part of a broader process of self-exploration. It's worth keeping an eye on Duncan as the model of an extremely enthusiastic early adopter of personal genomic technologies - the obstacles to understanding his genetic information will soon be things that the rest of us need to wrestle with as well.

Subscribe to Genetic Future.

Read the comments on this post...

Nobel laureate Paul Nurse on his family story

Sun, 21 Jun 2009 09:58:15 -0500

This is slightly unusual subject matter for this blog, but I found this presentation by 2001 Nobel Prize winner Paul Nurse absolutely fascinating. It's an account of his slow unravelling of his family background, told to an audience at the World Science Festival in New York last week.

The full video is beneath the fold:

Read the rest of this post... | Read the comments on this post...

Blogging conference presentations doesn't break Nature embargo

Fri, 19 Jun 2009 19:37:37 -0500

Added in edit: the original version of this post implied that the Nature editorial was recent, when it was in fact published in February this year; I was sent a link to it today and assumed it was new. I've edited the post to reflect this.

One of the major reasons for concern from presenters and conference organisers about the notion of conference bloggers is that having unpublished work discussed online may violate the embargo policies of journals and damage their chances of publication.

We do have clarification of this issue from one major journal. Nature has an editorial posted back in February that continues its long-term theme of encouraging scientists to engage in the blogosphere, and also includes this important statement:

At the same time, however, our cardinal rule has always been to promote scientific communication. We have therefore never sought to prevent scientists from presenting their work at conferences, or from depositing first drafts of submitted papers on preprint servers. So Nature journalists or those from any other publication should hear results presented at a meeting, or find them on a preprint server, the findings are fair game for coverage -- even if that coverage is ahead of the paper's publication. This is not considered a breaking of Nature's embargo. Nor is it a violation if scientists respond to journalists' queries in ensuring that the facts are correct -- so long as they don't actively promote media coverage.

Sounds good to me, and I hope to see similar clarification from other journals in the near future.

Subscribe to Genetic Future.

Read the comments on this post...

Free genome scans - but what's the business model?

Fri, 19 Jun 2009 19:31:28 -0500

Misha Angrist points me to the launch of TruGenetics, which basically looks like just another genome scan company with a unique gimmick: they're giving 10,000 scans away free.

What's the business model here? The registration page provides some hints:

Your questionnaire responses and genetic information will be used for genetic research. One of the main goals of TruGenetics™ is to develop a unique research database for conducting genetic studies. Your decision to use TruGenetics'™ services indicates that you are willing to contribute your questionnaire responses and genetic information to the TruGenetics™ research database. [...] TruGenetics™ may conduct this research, or may partner with another organization, including non-profit and commercial entities, to conduct research. TruGenetics™ may charge a fee for conducting research using this database.

[...]

You will not benefit directly from contributing your information to the research database. However, important discoveries might be made through this research, and this might significantly help other people. If these discoveries are validated and accepted by the scientific community, we will provide you with this information as it pertains to your genes. This research may also lead to the development of a commercial product. You will not receive any payments if this occurs.

Looks to me as though the business model here is pretty much the same as 23andMe's fundamental strategy - recruit customers, get them to provide both genetic and phenotypic data, look for novel associations and then (the tricky step) figure out a way to monetise said associations by selling them on to pharma or biotech companies. The only difference is that TruGenetics is willing to absorb more of a loss than 23andMe in developing that potentially saleable resource.

Ten thousand individuals is enough to power a reasonable genome-wide association study (GWAS) for one complex trait, or 2-5 moderately-powered GWAS for much more simple traits (e.g. drug response). Ideally, customers would be recruited on the basis of falling into specific phenotype categories (e.g. disease cohorts and healthy controls), so it will be interesting to see if customers have to fill in their phenotype survey before they are given any guarantee of receiving a free scan.

The big question is what genetic markers you could possibly find with 10,000 people that won't be scooped up by academic GWAS consortiums before you can finish your analysis and submit your patent applications. You'd need to target a phenotype that was sufficiently medically relevant to be worth selling, but simultaneously sufficiently obscure to not be the target of massive GWAS already in the pipeline.

Alternatively, perhaps the company is most interested in recruiting perfectly healthy individuals from specific populations to serve as a shared control group for disease-specific GWAS being performed by other groups; this could potentially be a fairly valuable resource. I'm speculating pretty wildly now, so I'll leave it there.

I've signed up, but I'll need to hear more details from the company before I commit to handing over my genetic and medical details. I'll let you all know when I do.

Subscribe to Genetic Future.

Read the comments on this post...

Dr Isis discusses conference blogging

Thu, 18 Jun 2009 19:38:54 -0500

Readers who haven't seen it already may be interested in the post and subsequent discussion on conference blogging taking place on Dr Isis' blog.

I feel that Dr Isis' post misrepresents my position in several ways (see this clarifying comment from me), but she does provide an interesting argument against the notion that "open tweeting" should be the default position unless the presenter explicitly states otherwise.

The discussion has given me an opportunity to clarify my thoughts on a few issues. Below the fold I've pasted some snippets from my comments on Dr Isis' post summing up some points I don't think I've ever fully spelled out here on my blog.

Read the rest of this post... | Read the comments on this post...

Creating a "blog-safe" icon for conference presentations: suggestions?

Wed, 17 Jun 2009 11:20:16 -0500

The rather contentious result of my live-blogging of the Biology of Genomes meeting last month made it very clear to me that the scientific community needs to do a better job of communicating in advance whether a presentation is off-limits to audience live-bloggers. I've since been involved in a number of discussions about this issue both on- and off-line.

Cold Spring Harbor Laboratory (the host of the Biology of Genomes meeting) has clarified its own position, stating that potential live-bloggers (or tweeters) need to explicitly seek permission from speakers before writing about their presentations. This fits with CSHL's policy of encouraging the presentation of unpublished data by preventing unauthorised reporting of results, but it puts potential bloggers in an awkward position: it's not always clear in advance which talks will be interesting enough to discuss online, and finding speakers before their presentation to ask them for permission can be both logistically challenging and socially awkward (especially in the cases where it requires explaining to the presenter what this "blogging" business is all about).

Far better would be a situation where presenters stated in writing whether they were happy for their work to be live-blogged in an official format: ideally, stating a preference would be part of the registration process for all attendees, and every entry in the conference abstract book (whether presentation or poster) would indicate explicitly whether the presenter was happy for their results to be freely discussed online. I hope that any conference organisers reading this consider setting up something along these lines for their next meeting.

In the interim, it strikes me that there is room for a more individual approach for speakers who are happy to have their work live-blogged: some sort of standard icon that could be added to a title slide or the corner of a poster, quietly indicating that the presented data is "blog-safe" - i.e. can be blogged/tweeted freely. Such an icon would obviously only be used by the small sub-set of researchers web-savvy enough to know about it, but it might nonetheless help to raise awareness of the issue among the broader scientific community.

The question is, what icon can we use?

Read the rest of this post... | Read the comments on this post...