Would you want to know whether your genes put you at a high risk for developing arthritis? I did. My youngest sister was diagnosed with rheumatoid arthritis as an infant, and my mother’s had RA for most of her adult life. Now in my early 30s, I’ve remained free of the disease, but given that I have another autoimmune condition, psoriasis, and am prone to weather-related joint aches, I’ve always felt that it was only a matter of time before I, too, would be diagnosed with RA.
That’s why I signed up to have my DNA tested through 23andMe, a direct-to-consumer genomics testing company. Along with Navigenics and deCODEme, 23andMe is one of a very small handful of for-profit direct-to-consumer companies that examine DNA for thousands of genetic variants, known as single nucleotide polymorphisms, or SNPs (pronounced “snips”).
All DNA is comprised of a four-letter code. The way those letters are shuffled in our genes determines what proteins are made by the body. An SNP is simply a one-letter change in a stretch of DNA – from AGCTA to AACT, for example. Most of the time, that one-letter difference won’t have any affect, but in some cases, SNPs can causes diseases, such as cystic fibrosis. In other cases, SNPs may play a role in how different people respond to the same medication, or they may simply be markers for regions of genes involved in disease.
For $429, the company mailed me a kit containing a small vial to fill with saliva. After I mailed it back, they examined the DNA in my saliva in order to create my “genetic profile,” which I accessed on their website.
The profile was extensive: in addition to revealing my predisposition for dozens of different diseases and conditions, including RA, osteoarthritis (OA), Sjogren’s syndrome, lupus and gout, it also revealed the regions my ancestors likely descended from, and a smattering of random traits, ranging from the curious (whether I can taste bitter food) to the potentially useful (whether I’m likely to be resistant to antidepressants).
23andMe makes it clear that not all the genetic information they provide holds the same significance. Instead, it divides health results into two groups: clinical reports, which are a list of diseases, conditions and traits for which there are genetic associations supported by multiple, large, peer-reviewed studies, and which have what they deem a substantial influence on a person’s chances of developing the disease or having the trait; and research reports, which are associations based on smaller studies that, in many cases, have not been replicated.
An Incomplete Picture
Because of my family history, my general practitioner and I have both long assumed that my genes must elevate my odds of RA. So imagine my surprise when my 23andMe clinical report concluded that I was at a below-average risk overall. Only one of the six RA-related SNPs that 23andMe examines indicated a high RA risk.
I wanted to believe that the results meant I’d won the genetic lottery – that unlike my sister, my knees would never swell to twice their size, and that unlike my mother, I’d never struggle to get out of bed on particularly cold and wet days. But when I spoke with Peter Gregersen, MD, who is head of the Robert S. Boas Center for Genomics and Human Genetics at The Feinstein Institute for Medical Research Manhasset, N.Y., he explained that unfortunately, I wasn’t exactly in the clear.
“The six SNPs 23andMe examines don’t offer a complete picture of RA disease risk,” explained Dr. Gregersen, who is also principal investigator at the North American Rheumatoid Arthritis Consortium (NARAC), a research institution jointly funded by the National Institutes of Health and the Arthritis Foundation. “There’s good research showing that all six of those SNPs are associated with an increased risk of RA. But to date, there are roughly 40 SNP regions linked with RA.”
According to Dr. Gregersen, those six, while based on sound scientific literature, only account for about 30 percent of a person’s genetic risk. In fact, while researchers continue to uncover new RA-related genes and SNPs every year, “we still haven’t explained nearly half of the genetic factors relating to RA ,” says Dr. Gregersen.
Plus, genetics aren’t the sole determinant in whether someone develops RA or not. Robert M. Plenge, MD, PhD, a clinical rheumatologist and a human geneticist at the Harvard Partner Center for Genetics and Genomics in Boston, says when it comes to RA, “Just 50 to 60 percent of risk is genetic; the rest is environment, and other factors that we don’t understand.” Translation: even if my genes were picture-perfect, I could still develop it.
A Few Downsides
For the many of conditions a personal genetics test screens for, there’s little to nothing you can do if you find that you have higher-than-average odds. That’s certainly the case for RA, says Dr. Plenge: “So you have an elevated risk. What then? There’s nothing you can do, other than not smoking, to try to lower your chances of getting RA.”
OA also falls under the “un-actionable” umbrella. “OA has less of a genetic component than RA,” says Emilio Gonzalez, MD, a professor of medicine and director of the division of rheumatology at the University of Texas Medical Branch at Galveston. Experts say about 30 percent of the risk of OA is probably genetic. “But even if a [genetic] test revealed that you had an elevated risk, the advice wouldn’t differ from what we tell everyone, regardless of their family history or genes: Keep your weight in check, don’t smoke, and exercise regularly.”
Experts also worry that consumers will arrive at incorrect conclusions based on their genetic test results: “A person could see that the test says she has a higher than average risk of, say, colon cancer, and be falsely alarmed – or conversely, she could see that she has a lower risk, be falsely reassured and choose to forgo crucial screenings such as colonoscopies based on those results,” says Charis Eng, MD, PhD, department chair of the Genomic Medicine Institute at the Cleveland Clinic Foundation in Ohio.
In a new paper in the American Journal of Human Genetics, Jason H. Moore, PhD, professor of genetics and of community and family medicine at Dartmouth Medical School, examined how personal genetic testing companies like 23andMe are using data to judge the health of their customers – and determined that personal genetic testing is, as he puts it, “very premature.”
“The scientific literature that [these tests are based on] is limited and not of much use for complex common diseases, including arthritis,” explains Moore. “They look at one individual genetic variant, instead of looking at interactions between multiple genetic variants and other factors, like environment, which we believe have a far more significant impact on disease risk.”
Moore had his own genetic material examined by 23andMe for the paper, and found the results gave him no more information than he could have gleaned from his family history.
If I had gone to see a medical geneticist, rather than doing a direct-to-consumer test, he or she would almost certainly not have recommended screening for RA or any other autoimmune disease says Clair A. Francomano, MD, director of adult genetics at the Harvey Institute for Human Genetics at the Greater Baltimore Medical Center. “A trained geneticist would take a very thorough family history and medical history, and based on that information, may recommend testing for one – or at most, a few – specific genetic variations for diseases that we might actually be able to make pharmaceutical, surgical or lifestyle recommendations for, like breast cancer or Parkinson’s disease. RA and most autoimmune diseases don’t fall in that category,” she explains.
The Good News
There are a few upsides to direct-to-consumer genetic testing: consumers who discover that they have an elevated risk for one of the handful of “actionable” health problems – such as type 2 diabetes, obesity and certain types of cancer – may be prompted to make healthy changes, such as quitting smoking, eating less and exercising more in order to reduce their odds of disease.
In addition, “Tests like 23andMe have made genetics less scary,” points out Gregersen. “Even four years ago, medical data panels were saying that genetic testing was risky for consumers, that insurance companies would use this information to deny people health insurance. Now, [experts and consumers] are more comfortable with it, because tests like 23andMe have made genetic testing more mainstream.”
Clearly, genes matter, which is why research institutes like NARAC exist. “We continue to conduct research because we think that genetic information may eventually help us understand what goes wrong in the bodies of people with arthritis,” says Gregersen. “And that will improve treatment, because we’ll know which genes make a person more or less receptive to specific medications and therapies.”
While every expert I spoke with for this story expressed excitement over the future of genetic research, not a single one said he or she would recommend direct-to-consumer testing for patients or family members. “You’d be better off getting a comprehensive family history – that is, going back at least two generations to find out which health problems your immediate members suffered from, and sharing that with your physician,” says Dr. Eng.
As for me, I found my genetic profile test results fascinating – but in hindsight, Gregersen summed it up best: “Direct-to-consumer tests are fun and interesting – but unfortunately, from a medical perspective, they’re not useful.”
Genes Associated With RA
The consumer genetic test offered by 23 and me looks at six genes and genetic regions that have been shown, in scientific research, to increase a person’s risk for rheumatoid arthritis. Most are involved with how the immune system works.
Two examples of genes included in the test include the HLA region and a gene called PTPN22.
The HLA region was one of the first regions of DNA found to be associated with rheumatoid arthritis, and it contains many genes involved in the body’s recognition of invaders. Researchers believe HLA may play a role in the development of many autoimmune diseases.
PTPN22 is a phosphatase that can reduce the activation and development of immune cells. Changes in this protein have been associated with other autoimmune diseases, including type 1 diabetes.
Can Genetic Testing Hurt Your Chances of Getting Health Insurance?
In a word: No. Direct-to-consumer genetic testing companies do not share your test results with anyone other than you. What’s more, last year, President Bush signed the Genetic Information Nondiscrimination Act (see genome.gov for more information), which specifies that health insurers and employers cannot discriminate against people based on their genetic information. It does not, however apply to other kinds of insurance, like life or long-term care; but some states have stepped in to provide that additional protection. For specifics on laws in your state, click here.