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