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DTC personal genomics

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170px-DNA_orbit_animated_static_thumb The New York Times has a piece up, I Had My DNA Picture Taken, With Varying Results, which begins:

I like to plan ahead; that much I knew about myself before I plunged into exploring my genetic code. I’m a healthy 28-year-old woman, but some nasty diseases run in my family: coronary heart disease, rheumatoid arthritis, Alzheimer’s and breast cancer.

So I decided to read the tea leaves of my DNA. I reasoned that it was worth learning painful information if it might help me avert future illness.

The author is a masters student in bioethics at Columbia (of curious note, her father is the designated heir of Ayn Rand and high priest of mainline Objectivism), so not the typical person off the street. That being said, the piece does reflect implicitly the almost oracular powers conferred to genetic data in the imaginings of the public. It is totally understandable, if somewhat concerning, that direct-to-consumer firms differ in their assessments. Even if the author had obtained a very high quality whole genome sequence, and had a large population sample to compare it against in terms of traits and genotypes, there’s only so much predictiveness you can squeeze out of complex traits. This does not mean that understanding the genetic underpinnings of diseases is without utility. Simply that there are limits to the confidence of predictions of common and complex diseases in the case of one particular individual. In fact, even if you are healthy, have no family history, and exercise, you can die of a heart attack in your 50s.

• Category: Science • Tags: DTC personal genomics 
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The last week has seen a lot of chatter about the slapping down of the diagnostic patent by Sequenom, Judge Invalidates Patent for a Down Syndrome Test:

A federal judge has invalidated the central patent underlying a noninvasive method of detecting Down syndrome in fetuses without the risk of inducing a miscarriage.

The ruling is a blow to Sequenom, a California company that introduced the first such noninvasive test in 2011 and has been trying to lock out competitors in a fast-growing market by claiming they infringe on the patent.

Sequenom’s stock fell 23 percent on Thursday, to $1.92.

The judge, Susan Illston of the United States District Court in Northern California, issued a ruling on Wednesday that the patent was invalid because it covered a natural phenomenon — the presence of DNA from the fetus in the mother’s blood.

The existence of intellectual property is a utilitarian one. That is, these are institutions which are meant to further the cause of creativity and innovation. Is there going to be an abandonment in this domain of the push toward technological innovation? Coincidentally in the last week of October Sequenom put out a press release which heralded some advances in its panel:

…The MaterniT21 PLUS test will begin reporting additional findings for the presence of subchromosomal microdeletions and autosomal trisomies for chromosomes 16 and 22, in addition to the previously announced additional findings for sex chromosome aneuploidies involving an abnormal number of the X or Y chromosomes. These additional findings complement the MaterniT21 PLUS test core identification of trisomies for chromosome 21, chromosome 18 and chromosome 13. With this expansion, the MaterniT21 PLUS test is the first-of-its-kind noninvasive prenatal technology (NIPT) to provide these comprehensive results from a maternal blood draw.

Sequenom Laboratories will begin reporting on these select, clinically relevant microdeletions, including 22q11.2 deletion syndrome (DiGeorge), Cri-du-chat syndrome, Prader-Willi/Angelman syndrome, 1p36 deletion syndrome, as well as trisomies 16 and 22 the last week of October. Results from a method validation study….

It seems that the firm’s main path to profit and riches is going to be to innovate faster, gain market share, brand recognition, and economies of scale. This seems as if it is a greater good for the public than its rents extracted through intellectual property monopolies.

• Category: Science • Tags: DTC personal genomics, Personal Genomics 
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Slate reposts a piece from New Scientist, Do You Really Want To Know Your Baby’s Genetics? It is arranged as a series of questions which might arise from the new information. For me my frustration with this sort of discussion is rooted in reviewing old articles about “test-tube babies” in major newspapers from the 1970s and early 1980s. Today in vitro fertilization is banal and commonplace, but many of the same concerns were voiced back then which you see cropping up now in regards to personal genomics. My issue is not concern as such, but its inchoate character. It is not uncommon for me to encounter people pursuing postgraduate work in science who express the opinion that “it’s scary,” the “it” being genetic information. When further queried the fear is generally layers upon layers of formless disquiet, some confusion about the specific details, as well as a default stance toward the “precautionary principle.”

With all due respect this isn’t rocket science. There’s no need to be overly general, the issues we’ll face are precise and specific, and often actually implicitly or explicitly enumerated in pieces such as the one above, which nevertheless manage to convey an air of murky foreboding. Unfortunately, not all of the issues are easily resolved, nor are they uncontroversial. For example I think abortion is actually a clear and distinct problem, because most of know where we stand on that. But what about the threshold for what constitutes a genetically normal individual? Frankly, most of us haven’t even really grappled with what that’s supposed to mean (to a great extent, I haven’t, and I probably think about these things more than the normal person). We marry, and we have children. So it’s been back to the dawn of time.

Ultimately this will not be decided by governments or bioethicists, if I had to guess. Rather, it will be decided by trial & error, the choices of individuals, and society’s response to those choices. There is no reason that everyone will take to these methods in the same manner, or to the same extent. Some people want to know everything, and some people would prefer to let the die fly. What’s the harm in allowing both stances, and all those in the middle, to flourish? What’s so concerning about knowing…or not knowing?

For myself, we are looking to the MaterniT21 PLUS test for the next pregnancy. At the least.

• Category: Science • Tags: DTC personal genomics, Personal Genomics 
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Genomes Unzipped points me to a Nature survey on personal genomics for scientific researchers. With price points down to $200 or so many scientists have been at least genotyped. Though it varies by domain. Many molecular biologists seem intrigued by the novelty of personal genotyping services. In contrast, in a room of a dozen or so population geneticists and the like nearly half are liable to have already gone through some service.

All that being said, I haven’t heard from people who want to make their genotype public in a long, long, time. Has the steam run out of that project? You might hear from me again with a subtle twist on this in the near future.

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I was having a discussion with some friends who have all expressed interest in being genotyped or have been about putting their information into the public domain. They were a pretty savvy lot (half of the six had been genotyped), but one expressed the common sense objection that “someone could find something in the future.” In other words, a really creepy stalker could keep running your data through Promethease. Imagine you’re a really strange person, and you have a bunch of gentoypes of people who you want to know about, and you design a program which scours the academic literature and constantly notifies you when the individuals in your database pop up with a large effect mutation. I have no idea why someone would do this. Perhaps you could be blackmailed by someone threatening to disclose to your employer than you had a 50% greater chance of a heart attack before the age of 60 than the general population? Whatever the details of the concern, they’re general, ranging from inchoate to eloquent.

But all this is moot in my opinion. I think in 10 years most people will probably have at least a genotype with the most informative SNPs. I assume that full genome sequencing will be really, really, common. I also doubt there’s just going to be one copy of this information. Right now digital security is not that great. People only care when there’s a breach. But in reality there are breaches far more often than people realize. Apparently it is common practice for technically savvy organized criminal gangs to exploit security holes at major financial institutions, steal personal data, and then blackmail the institutions by threatening to divulge the information. The institutions usually pay up, as the cost vs. benefit isn’t even close.

One can imagine similar things occurring routinely when genotype information spreads throughout poorly secured medical databases. All you need is one weak link, and it’s out. Right now if your credit card number is exposed because some hackers extracted them out of a leaky database, you call your credit card company and have the card cancelled. If someone gets your sequence you can’t have it cancelled. It’s out there. It’s yours. Forever (barring somatic mutations and ubiquitous gene therapy of some sort).

Of course they might get a sequence, but lack a name attached to it. This happens often with other data, which is why firms sometimes make a big show of having no “personally identifiable information” on file. But a genotype by its nature is personally identifiable. If they have a big database they might cross-check and look for matches. If they don’t find you, they might find relatives. Even if you are confident you aren’t exposed, it is possible a relative of yours is exposed, which would immediately give everyone some information about you in direct relation to your genetic relatedness.

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Direct-to-Consumer Genetic Tests Neither Accurate in Their Predictions nor Beneficial to Individuals, Study Suggests:

Direct-to-consumer (DTC) genetic tests give inaccurate predictions of disease risks and many European geneticists believe that some of them should be banned, the annual conference of the European Society of Human Genetics heard May 31….

Here’s the abstract for the talk which argued that DTC companies don’t give the best disease risk estimates:

Objective: Direct-to-consumer (DTC) companies predict risks of common complex diseases on the basis of genetic markers. Given the low number of markers involved and their small effect sizes, it is unclear whether high-risk groups can be identified. We investigated the risk distributions generated by two DTC companies for 8 diseases.

Methods: We simulated genotype data for 100,000 individuals based on published genotype frequencies. Predicted risks were obtained using the formulas and risk data provided by the companies.

Results: The table presents observed and trimmed ranges of predicted risks. The two companies used different formulas to calculate risks. One company predicted risks higher than 100% for 5 out of 8 diseases, which for AMD concerned 1 in 200 individuals. Observed ranges were smaller for the second company, except for Type 1 Diabetes. Predicted risks higher than 50% were frequently observed for company 1, but were exceptions for company 2. When predicted risks of company 1 were calculated using the formulas of company 2, observed ranges were substantially smaller.

Since I don’t put much stock in the small effect disease risk predictions currently, I am not surprised. But I’d be curious to look at the guts of their results. This was presented at conference, so some caution has to enter into the picture. The main issue I’d always want to emphasize with critiques of the lack of efficacy of DTC is that they need to be evaluated against the baseline of the limits to the efficacy of medical professionals and medicine in general. Genomics and DNA doesn’t make something magical, whether for good or ill.

The second presentation covered in the ScienceDaily release is kind of more disturbing to me. Here’s the abstract:

An increasing number of private companies are now offering direct-to-consumer (DTC) genetic testing services. The tests offered range from tests for single gene, highly penetrant disorders to susceptibility tests for genetic variants associated with common complex diseases or with particular non-health-related traits. The aim of this study was to collect information regarding the awareness, experiences and attitudes of European clinical geneticists about genetic tests and test interpretations sold directly to consumers. European clinical institutes where genetic counselling is offered to patients were contacted. One-hundred and thirty-one of the three-hundred eligible respondents (44%) answered a questionnaire. Eighty-six percent (110/128) of the clinical geneticists said they were aware that companies are advertising and selling genetic tests directly-to-consumers. Of the 44% (54/121) of the respondents who had been contacted by patients who underwent DTC testing, almost all respondents (98%, 47/48) did discuss test results with the patients. The following respondents somewhat or strongly agreed that DTC genetic tests should be legally banned for following tests: prenatal gender tests (69%, 77/112); genome scans (63%, 70/112), 54%, athletic performance (54%, 61/113), preconceptional carrier tests (53%, 59/112) and ancestry testing (27%, 30/113). The results indicate that most European clinical geneticists have only limited experience with patients who have accessed direct-to-consumer genetic testing, however, these physicians are entering into patient-physician interactions with patients when requested to do so.

I’m going to calm down, because these results frankly kind of piss me off. 30 out of 113 think ancestry testing should be legally banned? The stuff quoted in ScienceDaily is even more disturbing:

Genome-wide scans by companies are totally unacceptable, as they can derive sensitive information about medically relevant conditions and will also provide lots of information which is difficult to interpret, even for medical professionals,” said another respondent. Presenting the results of such tests directly to individuals is unacceptable, the majority of those surveyed said.

90% of respondents felt that a pre-symptomatic test — predicting if an asymptomatic person had a very high probability of developing a condition — should not be allowed without face-to-face medical supervision; 93% felt the same for a predictive test for a condition that has a penetrance (the proportion of individuals with the mutation who exhibit clinical symptoms) of 50 — 60%; 79% for a carrier test for homozygous monogenic disorders, such as sickle-cell anaemia; and 72% for a predictive test for a condition that increased or decreased a person’s risk of developing it by 4% when compared to the general population.

At the moment, DTC genetic tests reach the market without having undergone any form of regulation. “Better regulation is needed at the level of market introduction of these tests,” says Professor Borry. As in the case of drugs, a procedure should be developed for genetic tests.

I think one of the key issues is that these genetic professionals view DTC genomics in the same category as a pharmaceutical. I view DTC genomics as part of the same family of consumer and social goods as information technology. When viewed in the context of our current medical-industrial infrastructure it seems that on the margin the future opportunities to reduce morbidity through better lifestyle choices and more information via DTC genomics is a no brainer. If there was social science evidence that people who receive false positive results are regularly committing suicide then obviously my preference for loose regulation would need re-examination. That would be like someone jumping off the tenth floor of an office building after a “blue screen of death.”

But from what I’ve seen at places likes Genomes Unzipped and FuturePundit these dystopian visions of mass hysteria don’t end up to panning out. Until that point it seems that the best avenue toward improvement of this technology is to allow the trial and error process of innovation to continue. It is incumbent on those of us “in the know” to evangelize about the limitations and opportunities of this technology (e.g., don’t buy AIBioTech Sports X Factor!). But the reality is that much of medicine is already technology, and not subject to careful professional oversight. Instrumentation necessary for life critical functions are designed and built by engineers and technicians.

The bigger social issue here seems to be the attempt by genetic professionals to regulate the flow of information. Though I’m skeptical of most licensing regimes I’m not totally opposed to them on principle. But they need to be imposed on extreme cases only. You don’t want just any random person offering cut rate surgery or mass prescribing antibiotics to one and all. The individual and social costs of these actions can be very negative and irreversible (i.e., someone dies, or a resistant bacterial strain emerges). But when it comes to information services requiring a “professional” is going to choke the supply and spike up the cost. Additionally, there’s going to be a constant latency in terms of the ability of professionals to actually interpret the swell of data which is going to be coming in their direction. The reality is that the professionals are going to have to rely on advanced analytic software. Obviously my own preference is that such analytic software should be widely available and cheap. If you want to ban sex selective abortions address the problem at the level of abortion, a procedure which most people agree should be under some professional and regulatory supervision already. Don’t deny people the information to prevent a few harms.

If anyone wants to release their genotype into the public domain, email me at contactgnxp -at- Know that some clinical geneticists probably think you’re a public health hazard!

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I’ve been pretty vocal about the impending specter of genetic paternalism in relation to personal genomics, which I believe to be futile in the long term, and likely to squelch innovation in the United States in the short term. Like any new product category there’s a lot of hype and confusion in the area of personal genomics, but I think it’s important that we allow some mistakes and misfires to occur. Innovation and creativity isn’t failure-free.

With that said, I also think it is incumbent upon the personal genomics community, if there is such a thing, to “police” the flow of information. I have seen references in the media to a new personal genomics kit, Sports X Factor, selling for $180, from AIBioTech. My initial intent was to ignore this, as there is real science and tech to be covered. This is just another case of a biotech firm trying to leverage public confusion and gullibility into revenue. But if I think such a thing, I should make my opinion known, shouldn’t I?

So here’s the bottom line: If you don’t want to waste $180, don’t purchase a Sports X Factor kit, it’s just not worth the money. You can see a representative mainstream media report at The Washington Post. Because of the nature of how objectivity works it seems clear that they went looking for quotes from people who could express what’s going on here: this firm is hoodwinking gullible parents with a little extra money and time to throw around. The Sports X Factor kit is not worth the cost unless you want some psychic validation. The story strongly hints that some parents are just falling prey to confirmation bias.

Of course athleticism is substantially heritable. That is, how well you do does have a pretty significant basis in your genetics. But the most effective way to figure out your potentiality is free: look at your parents. The Sports X Factor test results summary page looks really confusing and quasi-scientific to me. More geared to impress customers with a barrage of numeracy than give cautious odds with huge error bars. How much of the variance in the population do these genes control? Not much last I checked. Three of the scientific references in the sample test results are to papers on which Dr Daniel MacArthur is a co-author. So let me quote some sage advice from him:

Beyond “the gene for speed”
I’m certainly not arguing here that genetics doesn’t play any role in Bolt’s success – or in the remarkable over-representation of West African descendents in Olympic short-distance track events, or the similarly impressive skew towards East Africans among marathon runners. In fact I think most geneticists would be staggered if this was the case, even though direct evidence for underlying genes is currently very thin on the ground.

Rather, my point is that an excessive emphasis on ACTN3 as a major explanation for Jamaican success does a grave disservice to the complex interplay of genetic and environmental factors required for top-level athletic performance. This suggestion goes against everything we’ve learnt about the genetics of complex traits from recent genome-wide association studies, which have revealed that quantitative traits (like height and body weight) are frequently influenced by dozens to hundreds of genes, each of small effect; if anything, it’s likely that athletic performance will be even more genetically complex than these traits. The ACTN3-centred argument also dismisses the importance of Jamaica’s impressive investment in the infrastructure and training system required to identify and nurture elite track athletes, the effects of a culture that idolises local track heroes, and the powerful desire of young Jamaicans to use athletic success to lift themselves and their families out of poverty.

It is almost certainly true that Usain Bolt carries at least one of the “sprint” variants of the ACTN3 gene, but then so do I (along with around five billion other humans worldwide). Indeed, I’m fortunate enough to be lugging around two “sprint” copies – but that doesn’t mean you’ll see me in the 100 metre final in London in 2012. Unfortunately for me, it takes a lot more than one lucky gene to create an Olympian.

The underlying science here does not buttress the marketing. If you want to fine tune your work-out, engage in personal self-experimentation and see what works for you! Ask your family members what their experience has been, they share your genes to a large degree. Genomics just isn’t going to add that much value. Allocate the extra money for personal training sessions or protein bars or something.

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Like John Hawks I get a fair number of questions from students. Some of them seem legit and I try and answer them, but sometimes they’re asking detailed things which would take me too long and it falls out of my task stack. And alas on occasion they’re clearly straight up asking me to write their paper from what I can tell. But today I got an interesting email from a doctoral student in England who found me via twitter and my blog, and was wondering if I could fill in an online survey for her research. It took me all of 5 minutes, so if you want to help them out (I’m thinking this is a painless way to increase someone’s sample size):

To fill in the survey, please:

Click here if you have bought a genetic test. (If you have bought a test but haven’t recieved your results yet, please still follow this link and just ignore any questions you can’t answer).

Click here if you are thinking of buying a genetic test.

• Category: Science • Tags: Blog, DTC personal genomics, Personal Genomics 
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Mischa Angrist and Brendan Maher point me to two interest personal genomics related stories. First, a follow up on inadvertent uncovering of incest story from last winter in GenomeWeb, Incidental Findings:

Recently, he and his colleagues encountered a case in which a married mother of three children with cognitive and developmental disabilities — the eldest of which she conceived in a previous union — opted to submit their genetic samples for screening. The researchers discovered a span of homozygosity that indicated the oldest child was the product of an incestuous conception between first-degree relatives. When they informed the mother of what they found, Beaudet says she vehemently denied such a relationship and demanded that the test be repeated. “The test was repeated and [the result] was the same,” he says. “And then she sort of broke down and said: ‘My husband will divorce me if he finds out about this.’ … There are just a lot of difficult things that come up.”

A few years ago professionals had discussions about whether they should even divulge this sort of information which might destabilize the family unit. In particular in relation to paternity. I think that’s a moot point, the horse has left the barn. Unless there’s a proactive effort by the powers that be to prevent consumers to from having any access to their own genetic information not facing up to these issues in the short run is probably just a matter of kicking the ball down the field. The only cases where I think it might be prudent would be when individuals have very short life expectancies, those with terminal conditions or the elderly. Otherwise you’re trying to run out a clock which will explode in your face.

Speaking of kicking the ball down the field, should children be tested for “adult” diseases? Some people think not, Parents ‘want child gene tests’:

Helen Wallace, from genetic science lobby group Genewatch UK, said: “Online gene tests frequently give misleading results because most common conditions such as cancer, obesity or diabetes are not predicable from a person’s genes, except in special circumstances.

“Children should not be tested for risk of adult-onset conditions, full stop. They should be allowed to decide for themselves, with medical advice, when they are grown up.”

Dr Vivienne Nathanson, director of BMA Professional Activities, said: “We would have concerns about genetic testing being widely available over the internet or off the shelf because parents could find out results without a health professional to help intepret them. They may also find out about genetic abnormalities for which there are no cures, or be caused needless worry.

From what I can tell GeneWatch UK is straight out of central casting for Left-science-neo-Luddite. In some areas vigilance is probably warranted, I’m not too sanguine about government intentions or execution either, but a lot of their material looks alarmist to the point of farcical. In any case, disease knows no hard and fast distinction between children and adults at age 18. I am going to get my children tested as soon as possible personally.

More information is not always better than less. But in most cases I think it is, and in the domain of personal health it almost always is.

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Dr. Daniel MacAthur & Dan Vorhaus offer their takes on the recent hearings in Congress on the direct-to-consumer genomics industry, A sad day for personal genomics & “From Gulf Oil to Snake Oil”: Congress Takes Aim at DTC Genetic Testing. I guess I lean toward light regulation. I don’t think that DTC personal genomics will result in systemic decrease in human happiness, and tight regulation will increase the costs of innovation and constrain access and reduce affordability. Though I guess that for some that’s a feature, not a bug.

My main point, which I think I got across on the Genomes Unzipped comments is that fraud, error and misrepresentation are rife across many health-related sectors in American society. The nutrition and diet industry are prime examples. Bad journalism on the health beat causes way more suffering than DTC genomics kits ever will, as people who are not intelligent make precipitous decisions based on the latest result which managed to slip through the p-value gauntlet and are sexy enough to be written up in USA Today. And, there are widespread distortions within our health care sector which really need to be addressed (I’m thinking in particular of frank talk about end of life palliative care). With that as the basis for judgement I don’t think that the fraud and misrepresentation one can find in DTC personal genomics is exceptionally worrisome or notable to warrant such attention or focus. This is an inefficient allocation of concern and regulatory resources, driven more by the industry’s puffed up claims and the apocalyptic projections of the skeptics.

Razib Khan
About Razib Khan

"I have degrees in biology and biochemistry, a passion for genetics, history, and philosophy, and shrimp is my favorite food. If you want to know more, see the links at"