Author Archive for Luke Jostins

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Friday Links: New genes for multiple sclerosis, and a new list of DTC genomics companies

12/08/2011
Categories: Uncategorized
Written by Luke Jostins and Daniel MacArthur

This week sees the publication of a large study of the genetics of multiple sclerosis. A consortium of 23 research groups gathered together data on nearly 10,000 MS suffers, and discovered 29 new genetic variants that contribute to disease risk. Overall, genetic variants for MS can now explain around 20% of the overall heritability of the disease, and these genetic variants highlight pathways that are likely to be important in the disease (such as T-helper-cell differentiation). Notably, this study is published in Nature, which is pretty rare for genome-wide association studies such as this. Perhaps related to this is the wonderful degree of detail included in the figures, such as in the ancestry plots of individuals in the study (see left). It is also surprisingly readable, containing just 4 pages of main article, with the nitty-gritty relegated to 100 pages of supplemental text. [LJ]

The Genetics and Public Policy Center have released an updated version of their list of direct-to-consumer genetic testing companies. You can view the list as a rather user-unfriendly massive PDF matrix of companies versus diseases tested here. The list is certainly not as useful as it could be – for instance, there are no indications of test price or quality, and whole-genome sequencing companies are shown as not testing for any disease, rather than (effectively) testing for all diseases – but it would be a good starting point for a crowd-sourcing project to produce a more comprehensive database. Hmmm… [DM]


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A case study in personal genomics

29/06/2011
Categories: Disease Risk
Written by Luke Jostins

I have no strong family history of any disease, despite having 7 blood aunts and uncles and countless cousins. So when I sent my spit off to 23andMe at the start of the Genomes Unzipped project, I was expecting something very similar to Caroline’s experience: a 5% increase in risk here, a 2% decrease in risk there, nothing that would really tell my anything about my health.

However, this was not my experience. Along with a pretty interesting Y haplogroup, I also had three unexpected and potentially worrying health results. I am a cystic fibrosis carrier, a hemochromatosis compound heterozygote, and have a strongly elevated risk of age-related macular degeneration. This cocktail of genetic disease certainly was not what I came to the test expecting!

After some thinking, I decided to take my test results to my GP, and see if there was any advice or testing he would recommend. In the end, my GP referred me to a clinical geneticist, which started a cascade of appointments which in turn led to a number of important changes in how I treat my own health.

What was most interesting is how the whole experience got me thinking about my health as something I am in charge of. I have since made a number of important life-style changes, some of them directly related to my genotyping results, some more generally to improve my overall health.

The point of this post is just to go through some of the experiences, what I have learned about specific conditions, and what changes I have made to my life since. In some sense, I feel like my experience is a case-study in what good outcomes can come from personal genomics, both for specific conditions, and more generally for how genetic data can change your own approach to your health.

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DTC Genetic Testing and the FDA: is there an end in sight to the regulatory uncertainty?

16/06/2011
Categories: Law and Regulation and Opinion
Written by Dan Vorhaus, Daniel MacArthur, and Luke Jostins

Disclaimer: Genomes Unzipped received 12 free kits from Lumigenix for review purposes, and Dan Vorhaus has provided legal advice to the company. We plan to release a full review of the Lumigenix service in early July.

Last month three direct-to-consumer (DTC) genetic testing companies opened their mailboxes to find a slightly ominous but entirely expected letter from the FDA. The three recipients (Lumigenix, American International Biotechnology Services and Precision Quality DNA) received substantively equivalent letters, with the FDA warning each company that its genetic testing service “appears to meet the definition of a device as that term is defined in section 201(h) of the Federal Food Drug and Cosmetic Act,” and that the agency would like to meet with company representatives “to discuss whether the service [they] are promoting requires review by FDA and what information [they] would need to submit in order for [their] product to be legally marketed.”

Translated from bureaucratese, that means that the FDA views these services as ones that may need to be formally reviewed by the agency and either approved or cleared before they can be legally sold. The FDA letter asks each company to describe its service and to explain either (1) why it does not require FDA approval or (2) how the company plans to pursue such approval.

This is a strategy that the FDA has pursued with a growing cadre of DTC service providers. These letters (currently 23 and counting1) represent the only public and company-specific actions the agency has taken to date with respect to DTC genetic testing. While many DTC letter recipients are engaged in dialogue with the FDA, those conversations have occurred beyond the public’s view. Until now.

Continue reading ‘DTC Genetic Testing and the FDA: is there an end in sight to the regulatory uncertainty?’


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

27/05/2011
Categories: Friday Links
Written by Luke Jostins

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


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

20/05/2011
Categories: Friday Links
Written by Luke Jostins

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]

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Calculating your Alzheimer’s risk

13/05/2011
Categories: Disease Risk and DIY
Written by Luke Jostins

For many diseases we have very little ability to determine who is at high or low risk; the risk factors are unreplicated, complicated, or understudied. However, for other diseases we can do much better. Alzheimer’s disease is a form of senile dementia that is characterised by abnormal clustering of proteins in the brain (right). We know a number of important risk factors for Alzheimer’s, and knowing your own risk factors may seriously change your estimate of the chance of developing the disease. But how can you calculate this risk?

This is going to be somewhat of an information deluge, as I go through everything to think about when you predict a complex disease, including how to calculate genetic and environmental risks, and how important these risks are, both individually and all together. I will demonstrate all of the calculations on the various GNZ contributors, and in particular how I have worked out my own risk.

I’ll measure the risks in terms of odds ratios; you may want to read the introduction to Carl’s post from earlier this year to refresh your mind on what this means. I will also use the disease probability; this is simply the chance of developing Alzheimer’s, or equally, the percentage of people with this set of risk factors who will develop the disease.

Also note that an important factor to consider is the baseline lifetime risk, the total proportion of people who will develop Alzheimer’s before they die. I am going to use a lifetime risk of 9% for men and 17% for women, taken from an Alzheimer’s Association report, but getting a good estimate of this is actually very difficult, and will vary from country to country.

If you want to know more about Alzheimer’s, including prevention, diagnosis and treatment, you can read about the disease on the Mayo Clinic or NHS Choices websites.

Continue reading ‘Calculating your Alzheimer’s risk’

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Last chance to submit comments to the FDA about DTC genetics

02/05/2011
Categories: Law and Regulation
Written by Luke Jostins

Today is the last day to submit comments to the FDA about the future of regulation of direct-to-consumer genetic testing, and, by extension, the future of personal genomics. I would strongly urge anyone reading this blog to submit a comment; the FDA needs to hear the full diversity of opinions and facts on this subject to make an informed decision.

Have you or your family taken a DTC genetic test, and can explain your experiences, either positive or negative? Are you a scientist working on human genetics and have thoughts about the scientific merits of the tests? Are you a clinician, and have insights into how individual’s having direct access to their own genetic information will effect your practice? Are you an ethicist, social scientist or public health professional with opinions about the rights of individuals to access their genetic data, or the impacts such access will have on society or public health? Write a hundred words or so and submit them to the FDA.

You can submit comments via this form; remember, today is the last day before comments close. You can see the comments that have already been submitted here.

For more coverage on this round of comments, see posts by Dan, Daniel and Razib. You may also like to reread our consensus statement about the FDA’s recent investigations.

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Inbreeding, Genetic Disease and the Royal Wedding

29/04/2011
Categories: In The News
Written by Luke Jostins

Today is, of course, the day of the Royal Wedding, with new blood entering the British royal line, and the hope of new heirs to our throne. And of course the question on the lips of all British geneticists is: will there be any new royal genetic diseases in this crop? The European royal lines have always been prone to the odd loss-of-function mutation. An unlucky mutation in Queen Victoria’s Factor IX gene caused a nasty case X-linked Haemophilia B in her male descendants (a mutation that was only mapped in 2009 by sequencing the bones of the murdered Romanov branch). Luckily for them, this mutation hasn’t been observed in any of Victoria’s descendants lately; while it can hide undetected in women, this obviously doesn’t apply to William. More systemic genetic problems have been the result of heavy inbreeding; Charles II of Spain, with his distressingly bushy family tree (left), suffered from severe Habsburg jaw, along with a host of other genetic complaints.

In terms of inbreeding, there has been a bunch of digging around in the press to find the closest common ancestor of William and Kate: Channel Four turned up fourteen and fifteenth cousinships, and the Daily Mail managed to find a eleventh cousinship. For comparison, William’s parents Diana and Charles were also 11th cousins, and the Queen and Prince Philip were a far more regal 2nd cousins once removed. Eleventh cousins share on average 60-parts-per-billion of DNA, or about 180bp (although with wide variation due to the spotty nature of meiotic recombination: in fact, 99.5% of 11th cousins will share no stretches of DNA through recent descent at all, while the remaining 0.5% will typically share tens of thousands of bases). Given that the average person harbours about 10 recessive diseases, this gives about a 1 in 1.6 million chance of Kate and Will’s offspring developing a royal disease due to a piece of DNA shared between them. So, not very likely then.

In fact, eleventh cousins is a pretty low degree of relatedness, by the standard of these things. A study of inbreeding in European populations found that couples from the UK are, on average, as genetically related as 6th cousins (the study looked at inbreeding in Scots, and in children of one Orkadian and one non-Orkadian. No English people, but I would be very suprised if we differed significantly). 6th cousins share about 0.006% of their DNA, and thus have about a 0.06% chance of developing a genetic disease via a common ancestor. Giving that the Royal Family are better than most at genealogy, we can probably conclude that the royal couple are less closely related than the average UK couple, and thus their children are less likely than most to suffer from a genetic disease. Good news for them, bad news for geneticists, perhaps?

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The genome hasn’t failed

21/04/2011
Categories: In The News
Written by Vincent Plagnol, Luke Jostins, and Daniel MacArthur

On Monday, the Guardian published an article by plant geneticist Jonathan Latham entitled “The failure of the genome”. Ironically given this is an article criticising allegedly exaggerated claims made about the power of the human genome, Latham does not spare us his own hyperbole:

Among all the genetic findings for common illnesses, such as heart disease, cancer and mental illnesses, only a handful are of genuine significance for human health. Faulty genes rarely cause, or even mildly predispose us, to disease, and as a consequence the science of human genetics is in deep crisis.

[...] The failure to find meaningful inherited genetic predispositions is likely to become the most profound crisis that science has faced. [emphasis added]

The claim that human genetics is in crisis is not novel. Latham made an extended version of this argument in a blog post at the Bioscience Resource Project in December last year, which Daniel critiqued at length at the time, and which contained a schoolboy statistical error corrected by Luke. And Latham is by no means the only genome-basher out there: the 10 year anniversary of the sequencing of the human genome triggered a spate of “genome fail” pieces (see Nicholas Wade, Andrew Pollack, Matt Ridley, and a particularly horrendous example from Oliver James, for instance).

We suspect for most of our readers Latham’s rather hysterical critique will fall on deaf ears, but it is part of a bizarre and disturbing trend that needs to be publicly countered. Here are several of the places where Latham’s screed gets it patently wrong:

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

18/03/2011
Categories: Friday Links
Written by Luke Jostins and Jeff Barrett

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]

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

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