How much should you know about your genes?

This summer, a panel of genetics experts did something surprising: they put out a list of genetic tests people should not get.

In the age of precision medicine, the genome is our oyster. There are cancer wonder drugs that pinpoint the errant genes that drive tumors. There are longstanding medical mysteries finally being unraveled by DNA sequencing. There is tremendous excitement over the coming age of treatments tailored to you. And there is also this: a very long list of genes for which the best medical understanding of what they mean for our health is essentially a shrug.

The poster child for the uncertainty underlying much of the information in this brave new world is a gene called MTHFR. It produces an important enzyme, but many medical geneticists simply sigh when they hear the gene’s clumsy acronym name.

This gene has made its way on to the do-not-test list more than once, because in almost no cases do the tests have any medical utility. Meanwhile, alternative medicine practitioners and Web sites have stepped up their claims that many people — perhaps anyone with a family history of any disease at all — should have the gene tested, because the information will help make them healthier.

“There’s all this excitement about genetic testing; President Obama talked about how precision medicine is going to empower all of us. So here you have these practitioners saying, ‘Let me empower you,'” said Timothy Caulfield, a professor of health law and science policy at the University of Alberta. “It’s this fascinating shift from science to bunk, and the shift is made very, very quickly, and often without any real sort of regulatory oversight.”

Here is the under-appreciated corollary to the new age of personalized medicine: just because you can do a genetic test, doesn’t mean you should.

There’s a natural human impulse to search for explanations for health problems, and the genome provides a powerful way to deepen that search. But in addition to the genuine promise that the genome brings, it also creates a niche where science can be exploited and vulnerable people seeking answers misled.

“It’s a ripe area for people to claim a scientific basis for stuff that may actually not be true at all, or may have a kernel of truth,” said Robert C. Green, a medical geneticist at Brigham and Women’s Hospital and Harvard Medical School. “We in genomics and society face a choice. Are genomes going to be so democratized and unregulated that we create an entirely fraudulent industry around them?”

Here is what people agree on: MTHFR is a gene that creates an enzyme involved in processing the vitamin folate and in recycling a blood chemical called homocysteine. The products of the MTHFR reaction are involved in lots of important bodily processes, such as DNA synthesis.

There are naturally-occurring variations in the gene that mean it functions less well in some people, sometimes causing high homocysteine levels. In early studies, those high levels were correlated with cardiovascular disease. That generated intense interest in the gene and studies of the common variants of the gene. But the balance of evidence has swung back to deem those tests of “minimal clinical utility,” according to the American College of Genetics and Genomics.

Where the disagreement begins is whether those naturally occurring variations — which are common, carried by as many as 40 percent of individuals in some ethnic groups — have a health effect.

For MTHFR, “there was this heyday of testing when we had all this preliminary data,” said Elizabeth Varga, a genetic counselor at  Nationwide Children’s Hospital in Ohio. Then larger, better designed studies began to show that the initial associations didn’t hold up.

“So really, the medical community has done an about-face, and that confuses people,” Varga said.

Genome pioneers have often bristled at the paternalistic idea that patients can’t handle knowing their genomes. But the MTHFR saga highlights something a little more nuanced than a person wrestling with the possibility that they are at elevated risk for Alzheimer’s disease. There are more than 3,000 published papers examining this one gene, often of varying quality, and in connection with a slew of frightening diseases. Critics of the test worry that someone without medical training may not understand how to evaluate the nuanced and often contradictory evidence.

Jenny Davis, 48, of West Chester, Ohio, sent her spit away to the company 23andMe because she’s interested in genealogy. DNA gave her another way to trace her family tree. But she also suffers from chronic fatigue and pain, and when she got her results back in 2013, she decided to see what else it might tell her and uploaded her results to be analyzed.

“I noticed I had this mutation and I was like, ‘What the heck?’ so  I started googling it,” Davis said. It was frightening at first, but Davis felt that the test helped her. She switched to a new vitamin supplement regimen and says she has much more energy.

But Amanda Webb’s quest to understand her 11-year-old daughter’s unidentified sickness has been less straightforward. Webb, 37, of Upper Arlington, Ohio, was alarmed when she found out her daughter carried two variants of MTHFR and wondered if it was the key to understanding her daughter’s frequent infections with walking pneumonia. She soon found herself surrounded by contradictions. Web sites had all sorts of information about the gene, but Webb was skeptical of much of it and found she had to be very picky about what she believed. She called Varga and learned, to her disappointment, that the test didn’t point to any treatment. When she went to holistic doctors, they told her to change her daughter’s diet and take more supplements.

“Unfortunately, there’s nothing that they agree upon,” Webb said. She will continue to seek answers and advocate for her daughter, but Webb said it is a tricky situation because “there’s no one there to help you, and that’s frustrating, as a parent.”

Half a dozen medical specialists contacted for this story said MTHFR testing doesn’t reveal actionable information and that while there may be occasional rare exceptions, it should not be done.

“It’s very easy to say it’s associated with everything. There are lots of small studies associated with psychiatric disorders, with depression, with not feeling good. … Obviously, it’s miserable not to feel good, so they’re trying to hang their hat on something,” said Charis Eng, chair of the Genomic Medicine Institute at the Cleveland Clinic.

But the test is still ordered by many physicians and sought out by patients. And there are many online forums and Web sites that say the information is useful. One source that many patients with questions stumble on is run by Ben Lynch, a naturopathic practitioner from Seattle. Lynch owns a company that sells supplements. He also runs MTHFR.net, a Web site that provides information about the gene and provides health recommendations — many of which are uncontroversial, such as eating more leafy vegetables and exercise. But he also recommends vitamin supplements, and acknowledged this was a conflict of interest in an interview.

Asked about the absence of large, randomized trials to back up his recommendations, Lynch described his research as drawing heavily on published scientific papers and his own knowledge of biochemistry.

“I’m saying we can’t wait for research to prove what I’m doing,” Lynch said.

The potential harms of people seeking out information about MTHFR may seem relatively small. People may pay for genetic tests or supplements that they do not need, and perhaps that money would be better spent on a gym membership or hiking boots, said Muin Khoury, the director of the office of public health genomics at the Centers for Disease Control and Prevention. But geneticists also worry about families that may decide that a gene is the cause of illness, causing stigma, more unnecessary testing or alarm.

“I think the biggest danger is for the family to ascribe all of this illness in a family and all the baggage that goes along with that to a [gene] variant that may have nothing to do with the underlying cause,” said Maren T. Scheuner, vice president of clinical genetics at the American College of Medical Genetics and Genomics.

But perhaps most worrisome is the fact that MTHFR isn’t alone.

“Right now, we’re at the stage where we can discover and study variation in genes at a much faster clip than we can understand what they mean,” said Lawrence Brody, director of the division of genomics and society at the National Human Genome Research Institute.

Asked whether there are other partially-understood genes where a confusing situation could arise, Khoury had a glib answer.

“Let me put it simply,” Khoury said. “99 percent or more of the genome falls there.”

This article is published in collaboration with Wonk Blog. Publication does not imply endorsement of views by the World Economic Forum.

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Author: Carolyn Johnson is a reporter covering the business of health. 

Image: Human genetic material is stored at a laboratory in Munich May 23, 2011. REUTERS/Michael Dalder