The official site of bestselling author Michael Shermer The official site of bestselling author Michael Shermer

23 and We

published August 2018

The limitations of personal genome service testing

Scientific American (cover)

Like a lot of baby boomers, I find myself gravitating to newspaper obits, cross-checking ages and causes of death with my current health parameters, most notably heart disease (which felled my father and grandfather) and cancer (which slew my mother). And then there is Alzheimer’s disease, which a 2015 report by the Alzheimer’s Association projects will destroy the brains of more than 28 million baby boomers. Given the importance of family history and genetics for longevity, I plunked down $199 for a 23andMe Health + Ancestry Service kit, spit into the little plastic vial, opted in for every test available for disease gene variants and anxiously awaited my reports. How’d they do?

First, the company captured my ancestry well at 99.7 percent European, primarily French/German (29.9 percent), British/Irish (21.6 percent), Balkan/Greece (16.4 percent) and Scandinavian/ Sweden (5.5 percent). My maternal grandmother is German and grandfather Greek; my fraternal great-grandparents were from Sweden and Denmark.

Second, the traits report correctly predicted that I can smell asparagus in my urine, taste bitter and have hazel eyes, ring fingers longer than index fingers, little freckling and straight, light hair. Third, for the disease reports, my eye lit on the phrase “variants not detected” for Parkinson’s, cystic fibrosis, muscular dystrophy, sickle cell anemia, Tay-Sachs and, most concernedly, Alzheimer’s. “Oh joy, oh rapture unforeseen!” (Thank you, Gilbert and Sullivan.)

But wait, 23andMe also says I have no bald spot, no cheek dimples, little upper back hair, a slight unibrow, no widow’s peak and a longer big toe—all wrong. If a genetic test for such comparatively simple physical features can be mistaken, what does that say about its accuracy for more complex diseases? “Our reports do not include all possible genetic variants that could affect these conditions,” 23andMe disclaims. “Other factors can also affect your risk of developing these conditions, including lifestyle, environment, and family history.” Oh, that.

For toe length, for example, 56 percent of research participants with results like mine (15 genetic markers for a longer big toe, 13 for a longer second toe) have a longer big toe, but I’m in the 44 percent. A prediction barely better than 50–50 isn’t terribly expedient. For Alzheimer’s, carrying the e4 variant of the APOE (apolipoprotein E) gene increases one’s risk of developing Alzheimer’s to 1 percent by age 65, 4 to 7 percent by age 75, and 20 to 23 percent by age 85 in men (to the same figure of less than 1 percent, to 5 to 7 percent and to 27 to 30 percent in women). Having two copies of the gene (one from each parent) moves the needle up to 4 percent (by age 65), 28 percent (age 75) and 51 percent (age 85) in men (2, 28 and 60 percent in women). But the test “does not include all possible variants or genes associated with late-onset Alzheimer’s disease,” so, for example, though lacking both e4 variants, I still have a 1 to 2 percent risk of Alzheimer’s by age 75 and 5 to 8 percent chance by age 85.

For further clarity on this tangle of interactive effects, I contacted Rudy Tanzi, a Harvard Medical School neurologist and head of the Alzheimer’s Genome Project, who co-discovered many of the genes for Alzheimer’s. He admitted that “no one can say with certainty [if ] a calculation of the variance of [Alzheimer’s is] due to genetics versus lifestyle,” adding that the e4 variant of the APOE gene “is present in 20 percent of the population and in 50 percent of lateonset cases but does not guarantee disease.”

Moreover, “until we identify all (or most) of the actual disease-causing mutations in these 40 genes, any attempts at putting an actual number at genetic variance is futile. In the meantime…, all we can say responsibly is that no more than 5 percent of gene mutations causing [Alzheimer’s] are guaranteed to do so. This means that in the remaining cases, most if not all almost certainly involve genetic influences (risk-conferring and protective), but in these cases (95 percent), it is an interplay of gene and environment/lifestyle that determines lifelong risk.”

What should we baby boomers do to shield ourselves against Alzheimer’s? “SHIELD” is Tanzi’s acronym for Sleep (uninterrupted seven to eight hours), Handle Stress, Interact (be sociable), Exercise (cardiovascular), Learn (“the more synapses you make, the more you can lose before you lose it,” Tanzi says), and Diet (Mediterranean: high in fruits, vegetables, olive oil, whole grains). As for personal genome service testing, actionable results with measurable outcome differences are still limited. But that is true for most medical knowledge, and yet we absorb everything we can for what ails us, so why not add genetics?

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5 Comments to “23 and We”

  1. ACW Says:

    An interesting column. However, it doesn’t deal with the issue that most worries me about the sudden craze for genetic testing, which is its link with ancestry research. If you watch the TV commercials for these services, they suggest that you derive not just certain tendencies and physical traits from your ancestors, but that your selfhood, your identity and culture, are largely inherited as well. Does this smell of the ideology that should have had a stake driven into its ugly black heart in 1945? (Maybe I’m sensitive because my grandmother was German. I never did ask her how she felt to have her husband — English — march off to fight the Kaiser, then to have her eldest son march off to fight Hitler (the other two, one of whom was my father, were fighting Tojo in the Pacific)).
    The TV commercials are sometimes amusing, as in the tongue-in-cheek account of a man who grew up thinking his family was German, joining German culture and dance groups, until the genetic test told him he was 51% Scots. ‘So I traded in my lederhosen for a kilt!’ Cute. More worrisome are the two commercials with black women who rejoice in the findings of their tests to show the regions of Africa from which their ancestors purportedly came. One buys a hat of traditional tribal fashion; the other claims her ‘foremothers’, purportedly leaders of a matriarchal tribe (? or was this ‘foremother’ a one-off, say, a widow succeeding a spouse?) bequeathed her her courage.
    Perhaps this is just the logical extension of ‘identity politics’, in which the label(s) stuck on you slot you into one or another pigeonhole which is supposed to define who you are. But I’m deeply uncomfortable with it. It stinks of rigid biological determinism.
    Moreover, although Mr Shermer knows whence came the various elements of his genome, for people such as the two black women in the ads perhaps especially, but for all of us to some degree, even assuming the accuracy of those genetic IDs, who can be sure where they came from? The black woman in the ad who lauds her foremothers (note that she picks and chooses which part of the pie chart she likes — that ‘foremother’ is only about 15%, and there is a far larger slice that presumably bequeathed her nothing much!) has no idea who that gene came from. It could be her foremother. It could also be a guy from a neighbouring tribe who burned her foremother’s village, raped her, and sold her to the white men in ships for a handful of beads and a bottle of rum. It could be a slave who was forced to ‘breed’ with her captive foremother to produce more slaves. For that matter, for any of us, that stray 15% could be the great-grandparent who looked suspiciously like the milkman or your great-great-grandparents’ best friend …. supposedly you need not go back more than four generations to find someone in your family nest raised a cuckoo’s egg.

  2. Johannes I. "Hans" Bakker Says:

    I enjoyed reading the original piece and the comment. It would be a great thing if more people took a university-level course in genetics and another one in history. Benedict Anderson has written very well about the social construction of the concept of a “nation” and the similar fiction of a “nation-state”. The UK, for example, is a conglomerate of many groups and hardly “British” in any scientific sense. The original inhabitants were pushed aside to some extent by the Angles, the Saxons, the Frisians, the Danes, etc. But even then, using those words is a short-hand since each of those groups was also a motley crew. I enjoyed Norman Davies book on invisible states, i.e. states like Burgundy that have been absorbed into a fictitious unity in a nation-state (e.g. France in this case).

  3. Fred Boland Says:

    Shermer’s article makes clear that genetics offer only a part (in most cases small) of the answers to complex questions of who we are. Nevertheless, I appreciate that small part’s contribution to the ongoing quest to ‘know thyself’, just as I appreciate knowing about the environmental factors that influence me. In the end, of course, I am some complex interaction of the two.
    I also derive satisfaction from having my data included in the many completed and ongoing scientific studies of various diseases and behavior. Scientific knowledge, for the most part, is a slow accumulation of knowledge and it is nice to be a part of ‘the big data picture’.
    Finally, I feel great that in almost all regards I am a rugged mongrel!

  4. Bad Boy Scientist Says:

    One concern I have about those DNA test services is that many require you to sign over the ‘rights’ to your DNA to that company. What that company can do with it after than is up to them.

    Skeptics should be encouraging people to not sign away rights willy-nilly (maybe we need lawyers to join scientists and physicians in skeptics groups).

    I attended a faculty meeting years ago in which we were _strongly_ encouraged to put our lecture notes and other intellectual products on social media to better connect with our students. They listed various social networks which would be good for distributing long documents, diagrams, tweet-length announcements, etc. One grizzled professor asked the presenter what the intellectual property agreements were for each of those social networks… the presenter hadn’t even thought to check.

    I’m not faulting Dr Mike – who is NOT advocating these DNA test services. But I think legal issues would be a nice complement to the flakey science of these services.

  5. Roy Latham Says:

    Interesting article. The message is that genetic testing doesn’t do much to help predict Alzheimer’s. It doesn’t both me that genetic testing as a social element is not discussed.

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