Archive for the 'Friday Links' Category

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Predicting lupus outcomes, US biomedical funding battles and telling children about genetic disease

There are a pair of papers in PLoS Genetics that shine some light on the effect of common GWAS variants on complex traits. The first investigates the effect of 22 common variants on sub-phenotypes of systemic lupus erythematosus, in how well a model including clinical measures plus GWAS variants can predict specific complications of lupus, over a model including just clinical outcomes. In some cases, there is little improvement (GWAS variants add nothing to prediction of renal failure, for instance), but in many there is a measurable improvement (such as for hameatological disorder and oral ulcers, the former of which is largely unpredictable from clinical outcomes). The second paper is a breakdown of the effect of the common obesity-associated variant FTO on BMI across age ranges; we see an interesting effect, whereby the variant that causes an increase in BMI in older children actually causes a fall in BMI in children under the age of 2. [LJ]

It’s budget battle season in the United States, and biomedical research funding looks likely to be caught in the crossfire. President Obama has proposed a $745 x 106 increase in the NIH budget, bringing it to $31.8 x 109 in total. This wouldn’t quite keep up with inflation, leading to a slight decrease in grant success rates from America’s largest biomedical research funder. The Republican-controlled House of Representatives, by contrast, has slashed the NIH budget by $1.6 x 109 in their proposed budget (bill HR1), which would be a heavy blow to research funding. Of course, scientists, non-crazy editorial writers and activist groups have been rallying around protecting research funding (in the NIH and beyond). Unfortunately I wouldn’t expect a speedy resolution, as veteran US politics blogger Nate Silver likens the whole situation to Zugzwang. [JCB]

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Ulcerative colitis genetics, Nature on the human genome

Yes, it’s Friday Links time yet again here at Genomes Unzipped.

A paper in Nature Genetics this week reports the results of a large meta-analysis of GWAS studies into ulcerative colitis, which more than doubles the number of loci known for the disease from 18 to 47. This pushes the proportion of heritability explained from 11 to 16%, and sheds more light on the shared and non-shared pathways between ulcerative colitis and Crohn’s disease, along with the interplay with other immune and inflammatory disorders.

The lead author is a Genomes Unzipped contributor, but he emphatically refused to contribute to this Friday Links post, on the grounds that he doesn’t want to blow his own trumpet. So, instead, here is a quote from the Sanger Institute’s press release:

“The genomic regions we have identified give us an insight into the biology underlying ulcerative colitis,” says Dr Carl Anderson, from the Wellcome Trust Sanger Institute and first author on the paper. “These important initial discoveries are the building blocks on which we can begin to derive better IBD treatments, though much further work is needed before these become a clinical reality.” [LJ]

Nature has a special issue this week devoted to the decade of progress since the publication of the human genome sequence. Eric Lander, who was first author on the original Human Genome Project paper, has a long and thoughtful commentary on the subsequent impact of that publication across a wide range of fields. Elaine Mardis accompanies Lander’s piece with a discussion of the astonishing advances in sequencing technology over the last decade (including a figure that emphasises the tremendous impact of the development of the Solexa/Illumina Genome Analyzer platform, which boosted sequencing capacity by eight orders of magnitude in a single year!).

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A decade of genomics, 60 new genomes, parenthood and sharing genetic data, and more on data return

To celebrate 10 years since the back-to-back publications of complete human genomes in Science and Nature, Science has published series of articles looking back at the last 10 years of genomics, and forward to the future. The article contains short essays from Francis Collins and Craig Venter, the former talking about some of the successes of medical sequencing (including giving a name and photograph to the exome-sequenced IBD patient I discussed a few weeks ago), and the latter discussing how far we still have to go before genomics can reach its potential. Baylor’s Richard Gibbs talks about how the large-scale technical discipline of genomics and the biological subject of genetics are starting to re-merge, after the Human Genome Project saw the two diverging, and there is an oddly inspiring comment from theologian Ronald Cole-Turning about how genomics is redefining our vision of humanity.

Of particular interest is an article by Eliot Marshall on why genomics hasn’t yet had a large effect on medical practice, and what needs to be done to allow the genomic revolution to trickle into medical care. He argues that scientists and doctors need to meet each other half way; scientists need to focus more on showing the direct clinical utility of genomics, whereas doctors need to be more ready to accept new technologies and discoveries, and adapt the way they practice medicine to make full use of them. [LJ]

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HiSeq doubles its output, a next-gen sequencing primer, and return of genetic data to patients

Illumina CEO Jay Flatley announced that an upgrade to their HiSeq 2000 platform expected this spring will allow users to generate 600 gigabases of sequence (the equivalent of 5 high quality human genomes) per one-week run of the machine. This would essentially double the current throughput of the platform and propel Illumina even further ahead in the arms race of delivering vast quantities of low cost sequence data. [JCB]

Over at Golden Helix, Gabe Rudy has just completed a three-part series introducing readers to the promise and challenges of new DNA sequencing technologies, which is well worth a read for those just starting out in the analysis of next-gen sequence data or who have a more-than-casual interest in the current state of the field. [DM]

This month’s edition of Trends in Genetics includes a review article on the ethical issues raised by the feedback of individual genetic data to research participants by Bredenoord and colleagues. This has long been a subject of debate, but the recent increase in studies that assay a large number of genetic variants (such as genome-wide association studies and whole-genome sequencing studies) has brought this issue to the fore. There is currently no consensus on how to deal with this, and in my experience the approach favoured has varied both between projects and between the ethics committees that have assessed them.

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Filling in the genetic map of South Asia, unexpected Jewish ancestry, and a new home for Genetic Future

Razib pointed us to the Harappa Ancestry Project, which is currently recruiting individuals of south and central Asian descent who have been genotyped by 23andMe, in an effort to fill in some of the notable gaps in the coverage of this region in maps of genetic ancestry. This effort follows on the heels of two similar projects focusing on individuals of European ancestry, Dienekes Pontikos’ Dodecad project and David Wesolowski’s Eurogenes BGA project. Both of these projects were featured in a recent article in Nature. Data from Genomes Unzipped members has been incorporated into both of these projects; if you’re a 23andMe customer willing to share your data, be sure to drop by and check them out. [DM]

For UK readers, there is currently an interesting TV show up on BBC iPlayer entitled Mad and Bad: 60 Years of Science on TV, which charts how science documentaries and science fiction have portrayed science, scientists and technology from the earliest days of television up to the present. One of the main themes was the conflict between the formal and usually old scientists looking for substance, and the media professionals who were looked for exciting fizzbang science. The somewhat heartening conclusion was that a new crop of scientists, such as Alice Roberts, Marcus du Sautoy and Brian Cox, have managed to reconcile these two strands, writing and presenting their own shows with a charisma that challenges that of professional TV presenters.

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From GWAS to pathways, the consequences of DTC genetics and screening by sequencing

A paper out in PLoS Genetics this week takes a step towards using genome-wide association data to reconstruct functional pathways. Using protein-protein interaction data and tissue-specific expression data, the authors reconstruct biochemical pathways that underlie various diseases, by looking for variants that interact with genes in GWAS regions. These networks can then tell us about what systems are disrupted by GWAS variants as a whole, as well as identifying potential drug targets. The figure to the right shows the network constructed for Crohn’s disease; large colored circles are genes in GWAS loci, small grey circles are other genes in the network they constructed. As an interesting side note, the GWAS variants were taken from a 2008 study; since then, we have published a new meta-analysis, which implicated a lot of new regions. 10 genes in these regions, marked as small red circles on the figure, were also in the disease network. [LJ]

23andMe customers will be interested in a neat little FireFox plug-in that allows them to view their own genotypes for any 23andMe SNP mentioned on a web page. You can download the plug-in here (you’ll need to have an up-to-date version of FireFox), and I have a brief review of the tool here. [DM]
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Friday Links

Nature ran an excellent story on the rise of genetic hobbyist-bloggers, featuring our own Joe Pickrell’s discovery of his Jewish heritage as well as the impressive efforts of bloggers Dienekes and David Wesolowski to explore human ancestry using publicly available large-scale genetic data, which finishes with a comparison by George Church between genomics blogging and the early days of social networks:

Church argues that better access to high-quality data could help this kind of informal bioinformatics to flourish, enabling computer-savvy people to make important contributions to genomics, just as they have with online businesses such as Facebook. “It didn’t take that much training to become a social-networking entrepreneur. You just had to be a good coder,” he says. With bioinformatics, “I think we’re in a similar position.”

Ion Torrent logoDNA sequencing news this week was dominated by the commercial launch of the fancy new machine from Ion Torrent and the announcement of $1 million prizes for home-brew improvements to the work-flow, throughput and accuracy of the embryonic platform. Nick Loman cast a skeptical eye over the output from the Ion Torrent PR machine, and particularly the competition, asking “Is this helping democratise sequencing, or is it a cynical tactic to get cheap R&D?” At the other end of the cynicism-naivete spectrum, Harvard molecular biologist Gary Ruvkun pondered sending an Ion Torrent to Mars to sequence the (hypothetical) DNA sprinkled across its dusty terrain.

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Friday Links

Hong Kong researchers have reported the first attempt to perform large-scale genetic analysis of an unborn child from the blood of its mother. The technique takes advantage of the fact that foetal DNA is found in small quantities in maternal blood; however, analysing this DNA is complicated by the fact that it is heavily contaminated by DNA from the mother (in a ratio of around 9:1). This means that while it is possible to identify the fraction of the foetus’ genome derived from the father, determining whether or not a specific variant has been inherited from the mother is extremely challenging.

Contrary to some media reports, the researchers didn’t succeed in (or attempt) sequencing of the foetus’ entire genome. Rather, they genotyped the parents at ~900,000 sites of common variation, and then estimated the foetus’ genotype at a fraction of those sites using next-generation sequencing of DNA extracted from the mother’s blood. Truly comprehensive analysis of the foetal genome would first require high-accuracy genome sequences of both parents, as well as extremely deep (and thus expensive) sequencing of maternal blood DNA. It seems likely thatin the immediate future foetal DNA analysis will be restricted mostly to targeted examination of specific disease mutations (a far more tractable problem), providing non-invasive detection of severe disease mutations in early pregnancy for at-risk families. [DM]

Over at Genomics Law Report, Unzipper Dan Vorhaus uses revelations from the WikiLeaks cables about US plans to obtain DNA and other biometric data from key world leaders to explore the currently muddy laws around surreptitious DNA testing. [DM]
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Friday Links

A quick note about the Reader Survey; we are going to stop taking responses at the end of Saturday (Pacific Time). If you haven’t already done so, please fill out the survey now.

A couple of interesting articles this week on the Personal Genome Project and public genomics in general. Mark Henderson at the Times has an opinion piece (behind a paywall, I’m afraid) about Misha Angrist‘s book Here Is A Human Being (see also this review from The Intersection), and in the Duke Magazine Mary Carmichael has an in-depth feature on the work of George Church, with some interesting history of the early days of the PGP.

One aspect that comes out of these articles is how those who take part in public genomics projects are starting to own the unknown unknowns. They accept that they cannot anticipate all the risks of making their data public, but are willing to take the risk of exposing themselves to these unknown risks, and in doing so turn them into knowns. Another aspect is the sheer number of individuals who want to sign up to have their data published online: 15,000 people have expressed interesting in being part of the PGP, despite initial NIH concerns the no-one would want to take part at all. This also chimes with research presented at ASHG this year, showing that members of the public are more concerned with contributing to scientific knowledge, and, crucially, getting access to their own genetic data than they are about the potential risks that such data could expose them too. [LJ]

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Friday Links

At the risk of turning Friday Links into a self-trumpet-blowing occasion, we are happy to report that a number of GNZ contributors (Jeff, Carl and Luke) are authors on a new Crohn’s disease GWAS meta-analysis of 6000 patients that came out in Nature Genetics this week. The study brings the number of Crohn’s associations up to 71, with 30 novel, bringing the proportion of heritability explained up to about 24%; also worth noting that all of the associations from the previous meta-analysis were replicated it this one, showing how the cross-platform independent replication experiments that are now standard have largely obliterated false positives in GWAS. There were also 5 loci that showed evidence of a second, independent signal, which I think is a promising sign of things to come.

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