How I got my genes tested, and the birth of Science Writer Disease Risk Top Trumps

By Ed Yong | July 21, 2010 9:00 am

23andmekit

Thanks to genetic testing, I now know that If it were biologically possible to have a baby with Mark Henderson, Science Editor of the Times, that baby would be certain to have wet earwax. And he or she would definitely not have cystic fibrosis. Science!

This is all in aid of a session at the UK Conference of Science Journalists exploring the world of genetic testing, hosted by Mark, Daniel Macarthur from Genomes Unzipped and others. As part of the session, various journalists were offered the chance to get their genes tested for free by one of the three leading companies providing such services. I had a brief chat to Daniel about it, got his recommendations, and signed up. Four days later, a testing kit from 23andme arrived on my desk. I knew that 23andme had recently swapped some samples in a technical blunder but after reading Daniel’s blog, I was convinced that it was unlikely to happen again. If it did, I would enjoy finding out that I was secretly a black woman.

An hour later, I had delivered a dollop of my finest sputum into the tube they provided… and realised that I was only about a third of the way up to the fill-line. Doing this in the middle of the office was not a smart move. Ten further minutes later, and to a crescendo of laughter from my colleagues, the tube was full, sealed in a biohazard bag (I try not to take this as an indictment of my breath) and sealed in a Fed-ex envelope.  Four weeks later, the results arrived. The whole process couldn’t have been simpler.

In fact, it was perhaps too easy. Signing up to the 23andme site, verifying the code on my testing kit and preparing the sample took little more than an hour. I had to read and agree to documents that reassured me about the privacy of my information and provide consent to analyse my samples. The same documents warn about the possible psychological consequences of finding out your data and the limtiations of the resulting information (more on these later; meanwhile, I’ve uploaded the full consent form to Posterous so you can see it for yourself). Nonetheless, I was well aware of these risks. I could have found out that I have substantially high odds of developing life-threatening diseases. I could have discovered that I’m not actually related to my parents. This is not a bottle one can re-cork.

But I grapple with issues of genetics and risk on a daily basis, both as a science writer and as part of my work at Cancer Research UK. I assumed that I would be sensible enough about my results to avoid any deterministic anxiety or any sense of false assurance. The results probably wouldn’t affect my behaviour in any material way and besides, my family history is (to my knowledge) largely free of any severe chronic illnesses.  But to be honest, the biggest driver was an irrepressible curiosity. Mark Henderson said it best when he first took part in a similar test:

“Perhaps a few thousand of the 6.5 billion humans alive today have yet had the privilege of finding out so much information about the DNA that makes them unique. Here was my opportunity to become an early part of the genomic age.”

So how does it feel to be one of these pioneers? Well, as it happens, fun but a little disappointing.

23andme provides two basic services for its customers – information about health and about ancestry. I’ll leave the ancestry element aside from now (I’m genetically close to people from East Asia – who knew?) The health aspects are more interesting. They’re based on an analysis of 550,000 sites across my genome, which vary from person to person by a single DNA letter. These variations (called SNPs) are small but significant – they can affect an individual’s risk of disease, traits from eye colour to earwax texture, and response to various drugs and chemicals. By profiling the SNPs, 23andme tells its customers about everything from their risk of cancer to their ability to resist malaria.

I click on Disease Risk and I’m faced with a league table of future ills. Conditions have been arranged into three groups, depending on whether my risk is higher, lower or comparable to average. All of these risk estimates are based on research – on massive “genome-wide association studies”  (GWAS) that identify SNPs behind specific traits. Each prediction has a confidence ranking, which reflects the size and number of studies that underlie the calculations. Importantly, each risk is presented in both absolute and relative terms, i.e. my actual risk of developing that condition, and my risk compared to other members of the population.

And here we hit the big snag. The “population” in this case generally refers to white Europeans or North Americans, because the vast majority of GWAS studies have been done in these regions. They are where the money to fund research and the willingness to sign up for it have been concentrated. This is a big deal because the link between SNPs and traits varies between ethnic groups.

As an example, the site tells me that I would have “slightly curlier hair on average” were I European. I’m not, so I don’t.  More significantly, it also tells me that I have roughly double the average risk of prostate cancer. That’s certainly worth knowing about – it would mean that I have around a 1 in 3 chance of developing the disease within my lifetime, compared to the 1 in 6 odds that most men have. But again, this only applies to Europeans. In fact, if I set the analysis to ‘African’,  I find that with exactly the same genes, I suddenly have a lower-than-average risk of prostate cancer. There’s no data for Asian populations. All in all, there are only a handful of results that I can rely on – I have an average risk of Type 2 diabetes (compared to the average Asian chap) but a slightly higher risk of rheumatoid arthritis.

I was aware of this before I signed up for the test, so my disappointment actually matches by expectations. However, things will change. Large genomic studies are underway in China and since 23andme regularly updates its information to account for new research, my reports should become a lot more interesting in time.

For the moment, there’s the odd useful nugget, veering from the useful to the humorous. I know that I am not a carrier for a variety of debilitating genetic diseases, from cystic fibrosis to Tay-Sachs disease. I’m told I have dry earwax, which I can confirm. I have “substantially higher odds of heroin addiction,” which I have no intention of confirming. Morbid fascination aside, there is a tremendous amount to play with on the site. If you had a mind to do so, you could interrogate your raw genomic data and scan your chromosomes SNP by SNP. You can even work out the odds of certain traits in a child between you and another 23andme user – hence the introductory quip to this post. The whole experience is presented through a seamless user interface and a permeating sense of fun.

This, perhaps, obscures more serious concerns. The ethnicity issue puts me in a somewhat enviable position, where results that could come as genuinely worrying can be easily brushed aside, leading to what Tom Whyntie called “the best version of Top Trumps EVER.”  But not everyone would be in the same carefree position. Mark, for example, has a higher risk of glaucoma that would probably have terrified me, had it appeared in my results. Given that my entire career and virtually all of my leisure pursuits are heavily dependent on vision, I have a potent fear of eye diseases.

The same applies to neurodegenerative conditions, which led me to discover my risk for Parkinson’s disease with some trepidation (it’s average, since you ask). When you first see your report, most of your health risks are plain as day, but a few select pieces of genetic data come “locked”. To uncover them, you have to make an active choice. Your LRRK2 gene, which affects the risk of Parkinson’s is one of them. Your BRCA1/2 genes, which affect the risk of breast, ovarian and other cancers, are on the list too.

There is a good reason why these have been singled out for secrecy. Unlike the other variants that 23andme looks at, which are common in the population and have small effects on our health, mutations in LRRK2 and BRCA1 are rarer but more dramatic. Before unlocking the LRRK2 information, the site tells you “You are about to learn whether you have a relatively rare mutation in the LRRK2 gene that raises your lifetime Parkinson’s risk to more than 50% compared to the population average of between 1% and 2%.” It’s a potential game-changer.

This sort of information can also ripple out to affect people who never consented to have their genes tested in the first place, such as close family members. If I had a high-risk LRRK2 variant, chances are that some of my close relatives would too. Imagine, as an extreme situation, what would happen if I had an identical twin. The “locked” status is understandable but it is the equivalent of a big red button that says “Do not press”. How many people would resist the temptation, especially if they have been curious enough to sign up to the service? To 23andme’s credit, it uses the opportunity to make people fully aware of what they’re letting themselves in for. Amidst a lengthy statement, it  tells you that not everyone with the high-risk version will develop Parkinson’s, nor does the low-risk version protect against the disease.

In fact, 23andme provides a consistently high standard of information. The original research papers that drive the risk predictions are all cited. Each trait or disease is accompanied by a lot of material – basic science, interviews with doctors, relevant posts by members of the online community, and even a timeline of relevant research. You also get practical tips for each disease, ranging from lifestyle advice to screening recommendations to contact details for relevant organisations. Judging by the cancer-related tips, these are all carefully crafted and based on decent evidence.

As mentioned, risks are presented in relative and absolute forms. This is important because a tripled risk may sound like a lot, but it’s less of a concern if it applies to a rare disease with a low background risk. You also get information in natural frequencies – an approach I like. For example, my report on rheumatoid arthritis tells me that in a group of 100 typical Asian men aged 35-79, 0.9 will get the disease. However, if all of them had my genes, 1.1 would get the disease. Nothing too much to worry about there.

But even here, there are potential problems with reliability. Mark Henderson has had his genes tested by three companies thus far – 23andme, DeCODEme and Pathway. In some cases, the three companies gave different results for the same stretch of DNA. In others, their reports gave different background risks of certain diseases. As Mark writes:

“If 23andMe is correct, then even though I have a high risk genetic variant, my overall risk of [glaucoma] remains low. If deCODEme is right, I have a one in three lifetime risk. And if Pathway is right, the population risk is low, but the peculiarities of my genome dramatically enhance my chances of getting it.”

These problems are inherent to the different companies, the tests they use and the information they provide. But further problems arise when that information enters the brains of the customers, where it often comes crashing against an inability to process information about risk. For all the careful phrases around risks and uncertainties, some folks are going to treat their report as nothing more than a sophisticated horoscope, given extra weight by the spectre of genetic determinism. For example, one brown-eyed community member was told that their genes predicted a high probability of having blue eyes with just a 1% chance of having brown eyes. They found the results “unsatisfying” and “confusing”. And this is a trivial example – the emotions that accompany a risk prediction for a severe disease must be even more potent, and especially so for people who aren’t well-versed in genetics.

Clearly, some will need more help than others at interpreting their results and that help will come at a premium. Not every jobbing health professional will have the knowledge to advise people about the implications of their genetic tests. Specialised genetic counsellors exist and 23andme will refer you to one, but you pay for the service out of your own wallet. This comes on top of the standard cost of the test, which would set the average customer back by $499.

I have mixed feelings about whether the cost is justified. The results are wonderful fodder for the curious and the confident but their limitations (especially for non-white ethnicities) prevent them from being of any obviously practical value to your health. This may change over time as more data flood in and the price starts to fall. But this doesn’t feel like a technology where there is a real benefit in being an early adopter.

Best possible result: “Mutant X-gene detected. Increased risk of superpowers, protecting world that hates/fears you”

Worst possible result: “Your ancestry is 50% Craig Venter”

Updated because I didn’t accurately reflect the contents of the consent statements, which I saved and are more informative than I remember, and on cystic fibrosis (see comment below)

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MORE ABOUT: 23andme, gene testing

Comments (25)

  1. Simon

    Best possible result: “Your majesty!”

    Worst possible result: “Ed, I am your father”.

  2. Great post Ed! I really enjoy these reports by science writers who try this kind of service, I think it’s a very effective way to explain personal genomics to people. Moreover, your warnings about the ethnicity issue could be very useful for new customers.

  3. Nox

    I signed up with 23andMe last year. I know a fair amount about genetics and statistical risks and I enjoy the site very much. My husband signed up at the same time so it was nice to see that (out of the things 23andMe tests for) we don’t have any looming, unknown recessive risks for potential children.

    Despite my abstract knowledge and lack of anything really awful in my report, I find their report on my eye color (they give me a 72% chance of blue eyes but my eyes are green) to be a useful reality check.

  4. It seems to me that absolute risk is more relevant than relative risk. This was fun to read, and I was curious about your results. However, it seems to me given the variability among testing companies and the worry factor, other than to satisfy curiosity, it isn’t of much use. Good health care would include testing for diseases where there might be higher risk anyway (like glaucoma) even without knowing about that specific personal risk.

  5. Although in future years it might be useful to people of Asian ancestry that China is currently building a database of info to draw from, I am queasy about how governments, especially those with a history of totalitarian behavior, will use information they gather.

    This is very informative, Ed, and I appreciate your sacrifice for the rest of us!

  6. Jackie Dropek

    I got my testing done through 23andme several months ago. Given a strong background and understanding of genetics I wasn’t too worried about reading too much into the results. I also have pretty thorough understanding of my family’s medical history and what we are generally at a higher risk for, as such it was mostly out of curiosity that I got tested. Overall I was very impressed. It accurately predicted all the things that were verifiable (yes it helps that my ancestry is that of most of those in the previous studies). It also told me I was at higher risk for pretty much all the things I knew ran in the family and a few things I’ve already been diagnosed with. Plus I was told I had a significantly higher risk of Type 2 Diabetes, which since I don’t have the usual lifestyle risk factors and weigh 110 lbs soaking wet wouldn’t have concerned me much until I talked to family and learned that it was much more common than I thought, even in those of us who are very tiny. So just something to pay a little more attention to than I would have otherwise. Mostly I was just happy to learn I’m not a carrier for any of the serious genetic illnesses.

  7. I’m sure if you asked Venter he’d tell you that your best-case scenario and worst-case scenario are actually one and the same ;-)

    [Brilliant! – Ed]

  8. This is the best reporting on this type of service I have read to date. Ed, this is just amazing. I wish everyone would read this.

  9. Not true. You can still have a child with cystic fibrosis even if you and your partner test negative with the 23andme array. Hence, this is the problem with how DTC genetic testing is misleading the public!

  10. Thanks Jonathan. Clearly asleep at the wheel there. A genetic counsellor also contacted me to make the same point. Her message:

    ” My name is Jordanna and I am a board certified genetic counselor, Co-founder and Director of Genetics for AccessDNA , an online consumer health resource focused on family health. We do not provide genetic testing services but evaluate DTC providers and provide easy to understand information on the genetics and inheritance of both rare and common diseases for consumers.

    I just read your article, “How I got my genes tests, and the birth of Science Writer Disease Risk Top Trumps,” and I really enjoyed it…as I usually do. I just one to point out a misconception about what a “negative” CF result from 23andMe really means. I know you were joking about having “a baby with Mark Hendersen,” but I have a lot of people are coming to me saying they cannot have a baby with CF because of a negative 23andMe test.

    As you are probably aware, there are over 1,000 documented mutations in the CFTR gene and 23andMe does not screen for most of them. Although the deltaF508 mutation accounts for 70% of CF cases in Caucasians, the 23andMe test does detect most of the non-Caucasian mutations. Basically, anyone, Caucasian or non-Caucasian, can still have a baby with CF.”

  11. Neuro-conservative

    Excellent reporting (as usual!). The fact that even someone as well-informed as yourself was able to casually make a mistaken inference about CFTR, is really quite telling, IMHO:
    1) The case for “paternalistic” federal regulation and requirement of intervening professionals is much stronger than the personal genome enthusiasts would have you believe.
    2) The case for reporting “clinical” results of genetic scans to participants in research studies is much weaker than is often argued under the principles of autonomy and beneficence.

  12. Great post!

    A note about BRCA1/2 (breast cancer genes) which you mention as one of the locked results. 23andMe only test for 3 BRCA SNPs (those that are common in Ashkenazi Jews) but there are hundreds of other BRCA mutations. I wonder if some people get false reassurance from a low risk BRCA result when they in fact have a mutation elsewhere in the gene?

    This could have serious consequences for those with a family history of breast cancer who may not then bother getting comprehensively tested for BRCA.

  13. at least you have the chinese & japanese sample in the hapmap as a plausible reference population. as it is, i’m told i’m “57% european and 43% east asian” when i’m brown ;-) but there are a bunch of gujaratis from houston being added to the hapmap so hopefully 23andme will update on that.

  14. In fairness to 23andme, the BRCA report says:

    “No copies of the three early-onset breast and ovarian cancer mutations identifiable by 23andMe. May still carry a different mutation in BRCA1 or BRCA2.

    And the cystic fibrosis report says:

    Does not have any of 31 CFTR mutations reported by 23andMe. Most likely no disease and not a carrier. May still be a carrier due to other mutations in the CFTR gene (not reported here).

    One can’t fault the provision of information somewhere. The issue is whether consumers will read their reports thoroughly enough or whether they stop at the main Carrier Status screen. Mine is just a list of genetic disorders that all have “Variant absent” under Status, and four lovely stars under “Confidence”. It looks very reassuring, to say the least, and perhaps falsely so.

  15. I’m astonished by the prostate cancer bit: I find it very hard to understand how the same gene could increase the risk of prostate cancer for Europeans and decrease it for Africans.

    Doesn’t really seem biologically plausible, does it?

    I wonder how robust the data on which those conclusions are based are? And by extension, I wonder how robust any of it (apart from the well known things like BRCA1 etc) is?

  16. Andy Williams

    Bloody fascinating article, Ed.
    Thanks for doing this.

  17. Doesn’t really seem biologically plausible, does it?

    epistasis?

  18. I signed up for 23andMe when they had their DNA Day special. Their offerings are pretty fun, but they only mention the safest of the results and don’t really get into info coming from the latest studies, etc. For the average person who may have a certain amount of trepidation regarding their results that’s probably not a bad idea, but I want to know everything. The thought of being susceptible to early-onset alzheimer’s is particularly terrifying to me, but if that possibility is there I damn well want to know. 23andMe isn’t touching that one, and actually doesn’t test for all the APOE SNPs (though I was told this was mainly due to poor resolution at that particular site).

    If you are also interested in seeing absolutely everything about genotype data, SNPedia has a pretty fantastic little tool called Promethease. It takes in data exported from 23andMe, deCODE and other services and exports a pretty comprehensive summary of all the SNPs that were genotyped and your variants. If it’s only a preliminary study or there is some debate, it talks about that as well. I actually found it far more interesting than 23andMe’s offerings.

    Promethease: http://www.snpedia.com/index.php/Promethease

  19. Paul Gerard

    In these times of infancy of genetic testing, there is is bound to be some potential for consumer confusion. I submit that there is potential for confusion, or at least disagreement as to the meaning of the test results, among professional genetic counselors. Nevertheless, savvy medical consumers are learning to pay attention to a number of medical tests including blood panels that disclose cholesterol levels by type (HDL and LDL ring a bell?), triglycerides, etc. I believe that the more you are involved with your own medical care, the better overall medical care you will end up receiving.

    I was diagnosed with type II adult-onset diabetes about 10 years ago. In the 10 years preceding that diagnosis, diabetes and “pre-diabetes” was simply not high on my medical risk radar — before the Internet and Wikipedia. However, had I known that I had a moderately increased risk of type II diabetes (even without knowing these statistically important proviso — what percentage of the risk is genetic in the first instance) I may have looked at my own pattern of consuming four or five soft drinks made with high fructose corn syrup and a nightly bowl of vanilla ice cream and made wiser choices. My physician provides online historical results of my cholesterol blood work in a graphic form. This kind of information has a salutary effect in involving me more acutely and intimately with my own healthcare. I believe genetic testing has a similar effect.

    One thing that you did not highlight is that genetic testing done by a reputable company like 23andMe is very much like a gift that gives on giving. Their geneticists and microbiologists keep up on current literature and medical “discoveries” regarding the SNPs tested by 23 and the company provides updated reports as to what these findings mean, if anything, to their customers. Information comes out in time frames of weeks and months, not years.

    Finally, even if this kind of genetic information is not meant to be of diagnostic medical value to consumers at this point, several companies have promised whole genome tests by 2013 for under $1000. I believe that getting a head start on the inevitable genomic information explosion is worth the initial confusion that the introduction of new technology always brings. I feel confident that terms like allele and SNP will become common parlance among most people in the next decade.

  20. Paul Gerard

    In these times of infancy of genetic testing, there is is bound to be some potential for consumer confusion. I submit that there is potential for confusion, or at least disagreement as to the meaning of the test results, among professional genetic counselors. Nevertheless, savvy medical consumers are learning to pay attention to a number of medical tests including blood panels that disclose cholesterol levels by type (HDL and LDL ring a bell?), triglycerides, etc. I believe that the more you are involved with your own medical care, the better overall medical care you will end up receiving.

    I was diagnosed with type II adult-onset diabetes about 10 years ago. In the 10 years preceding that diagnosis, diabetes and “pre-diabetes” was simply not high on my medical risk radar — before the Internet and Wikipedia. However, had I known that I had a moderately increased risk of type II diabetes (even without knowing these statistically important proviso — what percentage of the risk is genetic in the first instance) I may have looked at my own pattern of consuming four or five soft drinks made with high fructose corn syrup and a nightly bowl of vanilla ice cream and made wiser choices. My physician provides online historical results of my cholesterol blood work in a graphic form. This kind of information has a salutary effect in involving me more acutely and intimately with my own healthcare. I believe genetic testing has a similar effect.

    One thing that you did not highlight is that genetic testing done by a reputable company like 23andMe is very much like a gift that gives on giving. Their geneticists and microbiologists keep up on current literature and medical “discoveries” regarding the SNPs tested by 23 and the company provides updated reports as to what these findings mean, if anything, to their customers. Information comes out in time frames of weeks and months, not years.

    Finally, even if this kind of genetic information is not meant to be of diagnostic medical value to consumers at this point, several companies have promised whole genome tests by 2013 for under $1000. I believe that getting a head start on the inevitable genomic information explosion is worth the initial confusion that the introduction of new technology always brings. I feel confident that terms like allele and SNP will become common parlance among most people in the next decade.

    PS: New results today — leprosy susceptibility. Not anything to be worried or confused about, but interesting anyway.

  21. Jennifer Angela

    You can actually alter your genetics during your life time, right now, as you are living, due to a healthy life style (in a positive way) or a devastating life style (in a negative way). It´s not all about the way you were born. You can be born with a tendency to develop diabetes and yet never end up suffering from that illness if you stick to a healthy diet and have a healthy life style. Also, the “self-fullfilling prophecy” – effect all psychology fans among you will know, has a strong effect on your life. E.g.: If you find out due to genetic tests that you have a tendency to developing an eye illness and you will get extremely upset about it, certainly your eyes (as they contain endless amounts of nerve cells) will start stirring and your vision will become worse. If you assume: “Oh no, I am getting this horrible eye disease now!” – certainly you will get more upset, your vision will get even worse… you will be caught within a vicious circle. For that reason I advise people to just lead a healthy style (including a carefree attitude) and to let go of genetic tests concerning themselves, IF they are not convinced they really want to do those tests. Life itself is full of controlling, testing, observing and assessing powers anyway. Why controll, observe, test and assess yourself even more than you have been already? I need to add, that you don´t have to agree with me! It´s your own risk. If you insist on testing yourself genetically, just do it! If you feel you have no urge to hestitate, then I guess you really want to do it. But if you feel this slight discomfort within yourself at the very thought of assessing yourself due to your genetics, then don´t do it. I could think of so many reasons to avoid doing just that.

  22. Rebecca

    You cannot alter your genetics in a specific, directed manner through diet, exercise, or mindset. Alterations can occur in DNA; sunbathing for instance causes random double-strand breaks in DNA but the key word here is RANDOM. Specifically altering a gene has been done in model organisms. If you are reading this, chances are that you are not a laboratory mouse. Lifestyle does impact the effects of your gene products, but it cannot alter individual DNA basepairs in a directed (non-random) fashion.

  23. Heidi

    Jennifer, I’m going to disagree with two parts of your statement.

    The first disagreement I have is your statement that people can alter their genetics. My understanding (I’m definitely not a geneticist, but I do have a strong science background) is that you may be able to affect the expression of your genetics, but you can’t change what’s coded in your DNA. Perhaps that’s what you meant to type, but it’s not what actually got typed.

    The second disagreement is the idea that knowing more about your risk factors is negative. For people with some personality types, it’s certainly possible that finding out that they have an increased risk of something is going to stress them so badly that it actually increases the likelihood that that disease develops. Possible, but I have to admit that I’m pretty skeptical that it’s the most likely response people will have. I totally agree with your statement that a healthy lifestyle is important, but I think the reality is that most people pick and choose which aspects of “healthy living” they’re going to focus on. Some folks (including me!) may be more likely to focus on improving specific aspects of a “healthy lifestyle” if they have stronger evidence that their behavior is putting their health/life at risk. For example… I’m adopted, and in the last few years, I made contact with and gotten to know my birth mother. I also gained access to medical history info that hadn’t been available to me previously. I was always aware that keeping active, eating healthy, etc were important, and that it was important to not become overweight. However, it became much more “real” to me when I found out that obesity and obesity related illnesses were problems in my birth family. It made me much more aware of my weight- not in an obsessive way, but as something that I really DO need to pay attention to. Did I know previously that being overweight was bad? Certainly! But now I’m more aware of the risks associated with that little upward creep in my weight.

  24. Raj

    Great article. Many thanks for taking the plunge. After reading this article, I went to the 23andme website, and the pictures on the home page were of: a black woman, an asian man, and an asian baby.
    Quite honestly, that is a little misleading. I would actually have been quite keen to sign up, but thanks to your research I now know that they don’t have much of a database for Asians.

  25. That’s a very, very good point.

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