genomeboy.com

Thank you, James T. Kirkus. Note that the official pub date has since been moved up to 2 November 2010.

“If I’m to take a consumer genetic test, how do I know if I can trust the results, and should I be scared of what I might find out?”

Mary Carmichael of Newsweek asked me and a number of others to reflect on this question. And so I have.

• The short answer to the first part is, you may never be able to trust ALL of the results. Personal genomics companies type customers for several hundred thousand or a million variants (single-nucleotide polymorphisms or SNPs) and return results on a few hundred at most. My sense is that those few hundred are selected based on 1) the scientific validity of their association with particular traits; and 2) the presumptive interest of customers in those particular traits. But just because an association between a genotype and a trait is “real” doesn’t mean it’s predictive. Height, for example, is highly heritable, but it is probably mediated by thousands of genes. The other issue, as I’ve pointed out previously, is that the consumer genomics companies have thus far declined to issue standards. They use different SNPs in many cases. To assess multiple sclerosis risk at present, for example, 23andMe looks at two SNPs: one in a gene encoding a growth factor that sends signals to the immune system (IL7RA), and one that is tightly correlated with a SNP (HLA-DRB1) in the HLA complex, which is a region on chromosome six that harbors many genes involved in immune function. By contrast, Navigenics looks at those two plus another SNP in the IL2RA gene, which is important in T-cell activity and is a suspect in other autoimmune diseases. Both companies tell me that my lifetime MS risk is slightly lower than average, but the two numbers are not identical (23andMe: 0.24%; Navigenics: 0.17%). Meanwhile, a collaborative group of scientists has developed an algorithm incorporating 16 SNPs that is modestly predictive of MS risk. And SNPedia, the public wiki that collates SNP associations with human traits, lists more than 25 SNPs contributing to MS risk. Thus, the current level of confidence one can have in a SNP-based prediction of one’s chances of developing MS is weak at best.

• Should you be scared? Well, clearly in the case of MS, unless your neurologist tells you otherwise, you should not. But some consumer genomics companies return results on certain genetically mediated traits where the results are not so ambiguous. 23andMe, for example, returns results on three mutations that, if present, render women highly susceptible to breast and/or ovarian cancer. This is done on an opt-in basis: these data are not returned automatically with the rest of one’s 23andMe results. Some bioethicists believe that returning this information without explicit involvement of a doctor or genetic counselor is a bad idea. I do not share this view, but I understand it.

• Which brings me to my real take-home message: like most activities in life, personal genomics is not for everyone. I am not terribly interested in bungee jumping or climbing Mount Everest. Were I to let a friend talk me into doing either of those, assuming he wasn’t misleading me, then the onus would be on me for going along with it. But I’ve watched enough YouTube of bungee jumpers and I read Into Thin Air. Ergo, extreme sports and me: not happening. It is incumbent upon potential genome explorers to educate themselves before setting themselves up for possible disappointment and/or anxiety. I worry that critics of consumer genomics start from the assumption that would-be participants don’t know what they’re getting into and ultimately, cannot know, so, you know, let’s call the whole thing off. If you believe, as I do, that genetics education is in a sorry state and must be fixed, then advocating willful ignorance for everyone is both logically and morally indefensible.

• Okay, so who is personal genomics for? People who “opt in” should know upfront that:

• These are still very early days. The information attached to complex conditions controlled by many genes and the environment (like MS) is tentative and subject to radical changes in content and interpretation.
• Some information (e.g., possible high risk of breast cancer) may already be stuff you don’t want to know. “RTFM” as the kids say.
• The ideal personal genomics user is curious about the science, recognizes much of its tentativeness, and is an information seeker such that she won’t shy away from information that may not bode well for her future health.
• Sending a company $400 and spitting in a tube is not the only way to get involved. There are a bevy of research studies that involve personal genomic information. Take some time. See what’s out there, what’s involved, what your rights and responsibilities are, and what your expectations should be. This is your DNA and–unless you’re an identical twin–no one else’s. Do your own due diligence.

• Ask yourself what kind of person you are and why you would want to do this. Despite pressure from friends (and plenty of spam from Facebook), I’ve declined to join Facebook because I don’t like the way FB has handled its privacy policy and the contempt with which it has treated its customers. Plus, I find I already have enough trouble managing my online life; Twitter and email are about all I can handle, not to mention my book pages. Some social interactions make me anxious in a way that my genome does not. Your feelings may be the exact opposite of mine. And that’s perfectly fine: we shouldn’t need each other’s permission.

Personal genomics is, finally, personal. Look in the mirror and decide what’s right for you.

We are going to start hearing stories about people getting their entire genome sequenced. What might these stories miss?

One thing that they might do, is try to interpret the data the same way they did for companies like 23andMe and focus on common variants.

The real story is in the rare alleles. One in ten of us are very affected by these, and the sequencing tests reveal them as long as we are looking for them. Almost all common diseases have a rare allele component to [them]. What happened before is that we went through a fad. Scientists were looking where the light was in the common variants and they mostly ignored rare alleles.

(Hat tip: @DivaBiotech)

What’s the story behind your blog’s name?

When I told a friend I was getting my genome sequenced, she said, “Why you? What makes you so special, Genome Boy?” I thought that was funny.

What do you think the greatest challenges will be for individuals in the future, as the technology makes accessing personal genomes more affordable?

There will be many. One will be logistical: How do we manage all of this data about ourselves? Another will be learning to think probabilistically: What does it mean to have a 35 percent lifetime risk of Type 2 diabetes? This gets at a larger question: How do we retrain ourselves not to view genes as destiny? They’re clearly not - we are incredibly complex creatures affected by thousands of genes and an infinite number of environmental stimuli. But that’s a hard sell, and as a consequence, genes have been marketed as destiny. We have to get beyond that.

The GET Conference 2010 marks the last chance in history to collect everyone with a personal genome sequence on the same stage to share their experiences and discuss the important ways in which personal genomes will affect all of our lives in the coming years.

Tickets are pricey. This is a (long overdue, IMHO) fundraiser for PersonalGenomes.org:

We foresee a day when many individuals will want to get their own genome sequenced so that they may use this information to understand such things as their individual risk profiles for disease, their physical and biological characteristics, and their personal ancestries. To get to this point will require a critical mass of interested users, tools for obtaining and interpreting genome information, and supportive policy, research, and service communities.

Watch for a quick shot of the Personal Genome Project’s Joe Thakuria at 0:04.

Jason Bobe, DIYBio co-founder and Personal Genome Project Director of Community, on NPR:

RAZ: And so, are most of the people who are sort of these citizen scientists, I mean, are they actual scientists, or are they amateurs?

Mr. BOBE: It’s actually a wide range of different types of people. There are quite a few graduate students and professional scientists who moonlight as a citizen scientist. And we’re actually starting to see groups in various cities setting up laboratory space that’s a shared laboratory. They sort of pull their resources like clay potters have done with kilns or woodworkers have done with expensive lathes.

Listen to all of it here.

As “the first genomic generation” we will set the rules that many future generations may follow. Will we treat our genomes like our faces, which we share publicly even though they reveal details about our health, ancestry, and personality? Or will we be forced to hide them from view? Knowing our DNA could make us think of ourselves more mechanically, and yet increase our humanity by embracing our diversity. It could render us less mysterious, yet more awe-inspiring. Our genomes are a vast future resource. How we handle them will define us as a species—not as a fuzzy average, but with our individualism evident in detail.

- George Church in Newsweek

From a compelling story in the New York Times Magazine:

In an age of DNA, when biological relationships can be identified with certainty, it can seem absurd to hew so closely to a centuries-old idea of paternity. And yet basing paternity decisions solely on genetics places the nonbiological father’s welfare above the child’s. Phil Reilly, a lawyer who is also a clinical geneticist, has been wrestling with the policy implications of DNA testing for years, and even he is stumped about how society should manage the problem that men like Mike face. “We’re at a point in our society where the DNA molecule is ascendant, and it’s very much in the public’s consciousness that this is a powerful way to identify relationships,” Reilly says. “Yet at the same time, more people than ever are adopting children, showing that parents can very much love a child who is not their own. The difference here for many men is the combination of hurt and rage over the deceit, the fact that they’re twice beaten. I can see both sides of this argument. As a nation, we’re still in search of what the most ethical policy should be. Every solution is imperfect.”

The Personal Genome Project includes disclosure of nonpaternity as one of the explicit risks of participation. That said, having been warned is probably not much consolation to people who discover certain surprising things about their families.