Archive for the 'Friday Links' Category

Friday Links: Studying association studies, and success at last in psychiatric genetics

In PLoS Genetics this week there is a viewpoint article on data sharing in disease genetics. The authors systematically looked at 643 genome-wide association studies published between 2002 and 2010, to see how easily available the results of the studies are now. They found that the availability of full study results has gone down over time, and many groups that do share data have put more restrictions in place on its use. They put this down to fears over the privacy of research subjects, and in particular to the Homer et al study. The Homer et al result is somewhat complicated, but in essence it says that if you have stolen someone’s genotype data, you can use it to figure out if they have participated in any given research study by looking at the full results of the study.

It certainly seems possible that worries about privacy are reducing the free flow of information within the research community. However, whether on balance the decrease in information flow is worth the increase in security is an open question. For my own view, I feel that having the genome-wide results of genome-wide association studies freely available is very important to the field, and is more important than the the rather esoteric risk of someone stealing someone’s DNA and using it to figure out that they once took part in a research study of inflammatory bowel disease. [LJ]

Genome-wide association studies have been hugely successful in identifying dozens of common genetic risk factors for a large number of common diseases. However, one area that GWAS has not had much success in is the field of psychiatric illness, where finding common risk factors that replicate across studies has been consistently difficult. However, it looks like this is starting to change. The current issue of Nature Genetics has two papers from the Psychiatric GWAS Consortium, detailing some of the largest meta-analyses of schizophrenia and bipolar disease ever published.

The schizophrenia study robustly replicated two previously implicated variants, and discovered five new ones, and the bipolar disease study replicated one and discovered a new one. The new variants give us some pretty startling insights into the genetics of the diseases, in particular revealing the importance of a non-coding gene micro-RNA 137 in regulating a wide range of genes expressed in neurons. As always, these variants explain only a small proportion of the total genetic effect, but they show that psychiatric genetics has now truly entered the GWAS arena, with all the scientific benefits that this can bring to medical research. [LJ]

The images above, in order, are taken from the paper Temporal Trends in Results Availability from Genome-Wide Association Studies, and from Wikimedia Commons.

Friday Links: peer review discussions, attacks on newborn screening, and Google+

Joe’s post this week on the need for wholesale reform of the current peer-reviewed journal system caused a stir – following links from BoingBoing, Reddit and Hacker News it’s already our second most popular post ever in terms of traffic, and the comments thread currently sits at 86 comments. It’s (unsurprisingly) a topic that aroused passion among scientists, with strong arguments being made both for and against the current system. [DM]

A paper in Nature this week is that rarest of creatures: a high-impact genomics paper with only two authors. Heng Li and Richard Durbin show that the information contained in a single human genome sequence is sufficient to reveal a surprising amount of information about our recent evolutionary history. For the lay summary, Razib Khan has a typically thorough dissection of the paper and its implications. [DM]

Mary Carmichael has a fantastic piece in Nature (free registration required, annoyingly) about a Minnesotan woman who has devoted her life to attacking newborn screening programs. It’s a suitably balanced article: while the anti-screening activists engage in brazen hyperbole against a system that has unquestionably saved many lives, Carmichael doesn’t shirk away from noting that there have also been abuses of privacy. It’s not a debate that will be going away any time soon. [DM]

Colm O’Dushlaine, a scientist at the Broad Institute, has been analysing his 23andMe data in various ways and documenting his methods and results online. If you’re savvy enough to use the Unix command line you’ll find some useful tips for mining your own data. [DM]

Various Genomes Unzipped members have made the transition to Google’s much-discussed new social media platform, Google Plus. You can find Daniel here, Dan here, Joe here, Luke here and Vince here. [DM]

Genetics of CF severity, a survey of DTC customers and the value of a genetic diagnosis

In this week’s Nature Genetics there is a genome-wide association study of lung disease severity in cystic fibrosis suffers (or at least the subset who carry the ΔF508 mutation). The authors report a number of variants with “suggestive evidence”, and one with genome-wide significant evidence . The one genome-wide significant variant is rs12793173, with the C allele increasing the severity of lung disease. The variant is downstream of the gene EHF, which is also believed to play a role in asthma; the hope is that the function of this gene may shed some light on what causes variation in CF severity. As a CF mutation carrier with a CC genotype, any children that I have would be at a at slightly increased of having worse lung function. However, the variant only explains 1-2% of variation in lung function, so I won’t be worrying too much. [LJ]

A reader got in touch with us to inform of research he is doing into the response of personal genomics customers to genetic information. He is looking for users and potential users of DTC genetic tests to fill out a survey; you can find the survey here. If you have the time, this would be worth doing. Arguments about DTC genetics are too often based on hypotheticals or guesses, but there is a rapidly growing field that looks at how individuals really response to genetic data. This sort of data is exactly what is needed to make sensible decisions about the impact of DTC genetics on society. [LJ]

Continuing her series of interviews with people who have taken genetic tests, Elaine Westwick interviewed Jane Gregory, the mother of a child with a complex developmental disorder that was finally diagnosed by a genetic test. The interview raises a lot of the classical issues that you often see in clinical genetics cases, including the power of finding a genetic cause, even when knowing the cause doesn’t add any new treatment options. Well worth reading. [LJ]

The image at the top of the post, “65 Roses”, was made by Tanya Dawn

Cracking non-coding variation, carrying cystic fibrosis, and more Alzheimer’s prediction

Daniel and Luke attended the Biology of Genomes conference at Cold Spring Harbour last week. The talks did not have a huge amount of direct relevance to personal genomics, but did show some real quantum leaps in understanding the function of the non-coding DNA that makes up most of our genomes. Understanding mutations that lie outside of coding DNA is largely a prerequisite for transitioning to whole-genome sequencing for personal genomics, as most of the variation that drives genetic differences between people appears to lie there. As we’ve said before, one of the powerful aspects of sequencing is that it allows you to get at the aspects of your DNA that are unique to you, but that is only really useful (and a lot cooler) if we know what this unique variation does. Biology of Genomes showed us that that dream is closer now than it has ever been before.

For a (somewhat technical) account of some of the conference talks, you can read Luke’s blog posts over at Genetic Inference (along with a signficiantly less technical post about chipmunks and wood cabins), and Matthew Herper has a lay-friendly post on his Forbes blog. As has become standard, Twitter was an important way of disseminating knowledge live during talks, and Keith Bradnam and EpiExperts wrote about this aspect. [LJ]

Since GNZ started, Luke has actually been holding back writing about his many and varied genomics woes, and his resulting quest for bodily health, mostly for lack of time. However, one part of this has leaked out somewhat: he has recently given an interview to fellow blogger Elaine Westwick about being one of the two cystic fibrosis carriers in Genomes Unzipped. Read the interview at Elaine’s blog The Stuff of Life. [LJ]

On a similar subject to our recent post about calculating Alzheimer’s risk, over at Genomics Law Report Dan has written a detailed post about the regulatory challenges ahead for both direct-to-consumer and clinical tests for Alzheimer’s. [LJ]

Happy DNA Day! Here’s your Alzheimer’s risk

Friday Links is a roughly weekly collection of interesting genomics-related links scraped from the interwebs by Genomes Unzipped contributors.

Happy DNA Day! Cambridge members of Genomes Unzipped will be celebrating this evening in traditional British style with a beer or two at The Eagle, the pub in which Francis Crick famously interrupted the lunches of fellow customers to announce that he and James Watson had “discovered the secret of life” (actually the structure of deoxyribonucleic acid, but close enough).

Others are rejoicing in their own way. New York-based “brick artist” Nathan Sawaya, for instance, has built a massive sculpture of the the double-helical model out of LEGO bricks (left). [DM]

23andMe announced yesterday that it will now be releasing information on Alzheimer’s disease risk markers in the APOE gene to customers who purchased their recently upgraded v3 test. The APOE markers are famously associated with a major increase in risk for late-onset Alzheimer’s, with individuals carrying two copies of the ε4 version of the gene being around 15 11 times more likely than average to develop the disease. Customers who have been tested on the v3 platform will be able to able to access their APOE status after “unlocking” it; customers on earlier versions of the test will need to upgrade to get access. You can see screenshots of the unlocking and results pages here. [DM]

Using 23andMe to confirm identical twinnery, and a chance to tell the FDA what you think about DTC genetics

Over at Daily Kos, Michael Convente shares a fascinating story of using 23andMe data to pin down the precise relationship he has with his twin brother Matt. When Mike and Matt were born, the obstetrician told their mother that the presence of two separate placentas indicated that the brothers were non-identical (fraternal) twins – yet their incredibly similar appearance while growing up (see photo on left) suggested otherwise. Testing with 23andMe confirmed what the brothers had always suspected: that they are in fact identical twins. This is a useful reminder of the non-medical value of accessible genetic information: when it comes to unravelling these kinds of family mysteries, direct access to large-scale genetic data can be a powerful tool. [DM]

Readers who care about access to genetic information (i.e. all of you) and who are concerned about the potential effects of regulation on this access and on innovation in the field in general will soon have an opportunity to make their voices heard. Thanks to the efforts of Dan Vorhaus and others, the FDA has agreed to reopen the opportunity for public submissions while it deliberates on its next move following the agency-sponsored meeting on direct-to-consumer genetics last month. The submissions docket is apparently due to reopen today, and will remain open to submissions until the 2nd of May – so you all have a month to get your opinions in there. You’ll hear more from us about the process of submitting to the docket over the next week or so. [DM]

On a related note, genetic counsellor Christine Patch and academic (and Unzipped guest blogger) Barbara Prainsack have penned a response to the above-mentioned FDA meeting for BioNews. Patch and Prainsack provide a welcome note of nuance to the discussion; their final two paragraphs are worth quoting in full:
Continue reading ‘Using 23andMe to confirm identical twinnery, and a chance to tell the FDA what you think about DTC genetics’

‘Disguised’ heritability, changes ahead to marketing of personal genomics, deciphering developmental disorders

Even though genome-wide association studies (GWAS) have identified many loci associated with complex disease, much disease heritability is still unexplained, or “missing”. But what if rather than being missing, some of the heritability was “disguised”. This is the term put forward by Chris Spencer and collegues to describe the proportion of heritability that we miss because SNPs (imperfectly) correlated to the causal variant (“tag SNPs”) are used to estimate explained heritability rather than causal variants themselves. Reassuringly, their simulations show that for the vast majority of loci detected via GWAS the risk estimated from the best tag SNP is very close to the truth. They also show that, occasionally, fine mapping of GWAS loci will identify causal variants with considerably higher risk and this is more likely if the true effect of the locus is large. The figure above, taken from their paper, shows that for estimated relative risks in the range 1.2–1.3, there is approximately a 38% chance that the true relative risk exceeds 1.4 and a 10% chance that it is over 2. The consequence of all of this for personal genomics is that disease risk could be much greater than currently thought for those individuals who, for a given disease, carry a large number of common risk variants. [CAA]

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Analysing your own genome, bloggers respond to the FDA and more reporting on bogus GWAS results

Razib Khan, more known for his detailed low-downs of population biology and history, has written an important post on Gene Expression, explaining in careful detail exactly how to run some simple population genetic analysis on public genomes, as well as on your own personal genomics data. The outcome of the tutorial is an ADMIXTURE plot (like the one to the left), showing what proportion of your genome comes from different ancestral populations. This sort of analysis is not difficult, but it can often be hard to know how to start, so Razib’s post gives a good landing point for people who want to dig deaper into their own genomes.

This tutorial also ties in to some political ideas that Razib has been talking about since the recent call to allow access to genomic information only via prescription. If you are worried about losing access to your genome, one option is to ensure that you do not require companies to generate and interpret your genome. As sequencing, genotyping and computing prices fall, DIY genetics becomes more and more plausible. Learn to discover things about your own genome, and no-one will be able to take that away from you. [LJ]

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Inbreeding around the world, gene-environment interactions and sales of genetic tests

The picture above shows the relatedness of parents across different populations throughout the world; for reference, 0.065 is the average value for a first cousin mating. It comes from a paper out in pre-publication this week at the European Journal of Human Genetics, which estimates the level of inbreeding (or “consanguinity”) of parents by looking for sections of the genome where individuals inherit an identical piece of DNA from each parent. Such “runs of homozygosity” are a sure sign of inbreeding, as both parents will have inherited the bit of DNA from a recent common ancestor: the number and length of these sections can be used to find out how many generations ago the common ancestor lived, i.e. how closely related the parents were (cousins share a grandparent, second cousins a great-grandparent, and so on). In the plot above, we can see a high degree of cousin-marriage in Middle-Eastern cultures, and somewhat more sadly, high degrees of inbreeding in the Native American populations, due to the collapse in their population sizes. [LJ]

For those interested in gene-by-environment interactions the latest issue of Trends in Genetics includes a review article by Carole Ober and Donata Vercelli on the challenges of this area, illustrated by examples from asthma research. In particular they highlight the difficulties of moving G-by-E studies from examination of known candidate genes to genome-wide association. More interactions, this time of the protein-by-protein kind, are the subject of an article by Soler-Lopez et al. in this month’s Genome Research. They looked for interactions relating to Alzheimer disease using a combination of computational and experimental strategies, identifying 66 genes that putatively interact with known AD-related genes. The authors focus on the potential roles of neuronal death regulation and pathways linking redox signalling to immune response in AD pathology. [KIM]
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Defining a complete genome, innovative sequencers, and the mess ahead for personalised medicine

The Archon X Prize for Genomics offers a $10 million prize to to the first team that can sequence 100 human genomes within 10 days or less at a total cost of $10,000, with strict criteria for accuracy and completeness. However, given that there aren’t currently any gold standard genomes that could be used to confirm that a team has met the Prize’s requirements, and the complexity of judging the winner is far greater than for any previous award from the X Prize Foundation. To help refine the validation process, the Prize Foundation has just announced a collaboration with Nature to crowd-source ideas, which can be submitted via comments on the current plan over at Nature Precedings. If you’re interested in helping to define the state of the art in human genome construction, head over and have your say. [DM]

This week MIT’s Technology Review released this year’s TR50, a list of the 50 most innovative companies. Biomedical companies make a good showing, with 8 in total. Excitingly, three of these companies have been chosen for innovations in DNA sequencing technology; Complete Genomics, for developing the service approach to sequencing human genomes, Life Technologies for aquiring the new Ion Torrent machine, and Pacific Biosciences for their single-molecule sequencing machines. [LJ]

Over at Forbes, Matthew Herper pointed out the announcement of an exciting new targeted drug for cystic fibrosis that showed greater than expected results in clinical trials, as well as the announcement by Life Technologies of an impending upgrade to their Ion Torrent sequencing platform (also comprehensively dissected by Keith Robison here and here). This all sounds like good news, but Herper warned in a separate post that the implications of recent developments in genomics and pharmaceuticals might be heading towards a chaotic impact:
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