It’s Really Easy to Get Your Genetic Results. But Good Luck Making Sense of Them.

Direct-to-consumer genetic tests make DNA information more accessible and affordable. But no one can really be sure what to make of the results.

National Journal
Sophie Novack
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Sophie Novack
Nov. 8, 2013, midnight

A ge­net­ic test a few years ago told Cath­er­ine Afar­i­an and her hus­band that their fu­ture child would have a 50 per­cent chance of in­her­it­ing brown eyes, 30 per­cent of hav­ing green eyes, and 20 per­cent blue. That same test in­dic­ated that she has a de­creased risk for Alzheimer’s, and an in­creased one for colorectal can­cer.

Afar­i­an’s “ge­net­ic ex­per­i­ment,” as she calls her son, un­sur­pris­ingly ended up with brown eyes. Her risk res­ults though were a bit un­ex­pec­ted: the Alzheimer’s res­ults were a re­lief be­cause she has a fam­ily his­tory; the can­cer res­ults were a good thing to know be­cause she doesn’t.

Afar­i­an is the spokes­per­son for 23andMe, a privately held dir­ect-to-con­sumer, or DTC, ge­net­ic-test­ing com­pany based in Sil­ic­on Val­ley. The com­pany is at the fore­front of a grow­ing move­ment to bring the rap­idly evolving world of ge­net­ics in­to the hands of con­sumers, mak­ing their in­form­a­tion ac­cess­ible and af­ford­able for the first time.

“As a com­pany, we fun­da­ment­ally be­lieve your DNA is yours, you own it, and you should have ac­cess to it,” she says. “It’s our mis­sion to tell you everything sci­ence can.”

However, when it comes to ge­net­ics, sci­ence doesn’t know everything. And since what sci­ence can tell us about ge­net­ics is con­stantly chan­ging, ac­cur­ate in­ter­pret­a­tion of the res­ults is po­ten­tially out of step with the rap­id growth of test­ing tech­no­logy.

23andMe and the World of Ge­net­ic Test­ing

23andMe and oth­er DTC ge­net­ic-test­ing com­pan­ies have boomed in re­cent years, with hun­dreds of thou­sands us­ing the ser­vices to learn about their DNA. In 2007, 23andMe’s first gen­ome ser­vice cost $999 and provided 14 ge­net­ic re­ports; today it is $99 and of­fers 254 dif­fer­ent re­ports. 

These re­ports are lim­ited to dis­eases or con­di­tions that re­search­ers have some in­form­a­tion about. 23andMe of­fers re­ports in four cat­egor­ies: car­ri­er status, dis­ease risk, drug re­sponse, and traits. These range from cyst­ic fibrosis to Par­kin­son’s to an­ti­de­press­ant re­sponse to sex-hor­mone reg­u­la­tion. “As­paragus meta­bol­ite de­tec­tion,” un­der traits, will rank the odds of smelling as­paragus in your ur­ine.

“As­paragus meta­bol­ite de­tec­tion,” un­der traits, will rank the odds of smelling as­paragus in your ur­ine.

A ge­net­ic test through a doc­tor would typ­ic­ally be either a spe­cif­ic test for a spe­cif­ic muta­tion to con­firm a dia­gnos­is, or a broad­er dia­gnost­ic test look­ing for mark­ers across the gen­ome as­so­ci­ated with dis­ease states. But 23andMe ana­lyzes about 1 mil­lion of the more than 10 mil­lion single nuc­le­otide poly­morph­isms in the hu­man gen­ome and re­ports find­ings for a range of char­ac­ter­ist­ics. 

Se­lect­ing cer­tain SN­Ps from the gen­ome helps 23andMe keep costs low. Con­sumers simply mail in their saliva and 23andMe sends it to a cer­ti­fied lab. Two to four weeks later, the re­ports are avail­able se­curely on­line.

“The as­sump­tion is that at some point [23andMe] will move to whole se­quen­cing — but at a price point for con­sumers,” Afar­i­an says. 

The growth of these con­sumer tests holds great sci­entif­ic prom­ise, but also raises the ques­tion of un­cer­tainty on the in­ter­pret­a­tion side.

For 23andMe, in­ac­cur­acy in the test­ing is not a con­cern. “The in­form­a­tion 23andMe provides is in­cred­ibly ac­cur­ate,” Afar­i­an says. “If we tell you you’re a C-C there, you are. From there, the next step is in­ter­pret­a­tion — what does sci­ence know about it?”

It turns out the an­swer isn’t so clear.

(In)ac­cur­acy of In­ter­pret­a­tion

“There is a huge gap in in­form­a­tion about ge­n­om­ic ser­vices,” says James O’Leary, chief in­nov­a­tion of­ficer at Ge­net­ic Al­li­ance, a non­profit ad­vocacy or­gan­iz­a­tion ded­ic­ated to trans­form­ing health through ge­net­ics. “New tech­no­lo­gies de­vel­op quickly and it’s un­clear to people how to ac­cess them, what the pur­poses are, and what is reas­on­able in terms of res­ults.”

Even if the tests them­selves are ac­cur­ate, it’s im­port­ant for con­sumers to take much of the in­ter­pret­a­tion with a grain of salt.

“There is a huge gap in in­form­a­tion about ge­n­om­ic ser­vices.”

“Every­one will have res­ults. Every­one has muta­tions. Wheth­er they are med­ic­ally ac­tion­able or not is a dif­fer­ent story,” O’Leary ex­plains.

Not only are muta­tions not ne­ces­sar­ily in­dic­at­ive of a con­di­tion, they’re just part of the story. “A lot of the in­form­a­tion that is giv­en back to pa­tients on those types of life­style im­pacts of ge­net­ics are not very in­flu­en­tial risk factors,” O’Leary con­tin­ued. “The ge­net­ic por­tion doesn’t ac­count for a large por­tion of risk; ge­net­ic in­form­a­tion doesn’t make a lot of sense without oth­er life­style and en­vir­on­ment­al factors.” 

Afar­i­an re­cog­nizes the lim­its as well. “It’s the ba­sic nature of ge­net­ics that there are very few cases where ge­net­ics are de­term­in­ist­ic, mean­ing if you have a gene, you will have the con­di­tion,” she said. Her son could have had blue eyes, and Afar­i­an’s risk factor res­ults don’t mean that she will or won’t get those dis­eases. “At the end of the day, age is the greatest risk factor for Alzheimer’s. Fun­da­ment­ally, if you don’t want to get Alzheimer’s, don’t get old.”

In rare cases, however, muta­tions are in­dic­at­ive of far high­er risk, and are med­ic­ally ac­tion­able. An oft-cited ex­ample is a harm­ful muta­tion in the BRCA1 or BRCA2 genes, which greatly in­creases the risk of de­vel­op­ing breast or ovari­an can­cer. This is the muta­tion that fam­ously caused An­gelina Jolie to get a pre­vent­at­ive mastec­tomy earli­er this year. Where­as in many cases muta­tions will only in­crease risk by a frac­tion of a per­cent, a muta­tion on the BRCA1 or BRCA2 genes in­creases the risk sev­er­al-fold. If there is a fam­ily his­tory of can­cer that sug­gests someone may have a muta­tion in one of these genes, he or she can take a ge­net­ic test to check, and then de­term­ine how to man­age their risk.

BRCA1 and BRCA2 re­ports are offered through 23andMe, but it is a more lim­ited screen­ing. Since a fam­ily his­tory can de­term­ine wheth­er an in­di­vidu­al ought to take the ge­net­ic test at all, and be­cause it is a com­plex and ser­i­ous ill­ness, BRCA test­ing is prob­ably bet­ter suited for a doc­tor-ad­min­istered ge­net­ic test.

Re­cre­ation­al or med­ic­al?

While much of DTC ge­net­ic test­ing began largely for en­ter­tain­ment — traits like eye col­or, hair type, ear­wax con­sist­ency — the grow­ing em­phas­is on com­plex health and dis­ease factors could make the know­ledge gap a great­er con­cern. 

“It’s im­port­ant to re­cog­nize that for many people this truly is ‘re­cre­ation­al ge­net­ics,’ ” says Howard Levy, an as­sist­ant pro­fess­or in the Di­vi­sion of Gen­er­al In­tern­al Medi­cine and McK­usick-Nath­ans In­sti­tute of Ge­net­ic Medi­cine at Johns Hop­kins Uni­versity. “If they’re get­ting the data and mak­ing med­ic­al de­cisions without med­ic­al coun­sel­ing, that could be a prob­lem. If it’s just cool stuff to know — track­ing an­ces­try, cock­tail-party con­ver­sa­tion, for fun — and they are not mak­ing med­ic­al de­cisions, maybe that’s not a bad thing.”

However, the fact that 23andMe res­ults in­clude all types of con­di­tions means con­sumers are get­ting both “en­ter­tain­ing” and health care-re­lated re­ports.

“Be­cause so many res­ults are of un­cer­tain sig­ni­fic­ance, it’s an in­cred­ibly chal­len­ging thing to deal with and fig­ure out what it means as a con­sumer,” O’Leary says. “We’re find­ing out new in­form­a­tion about the gen­ome all time; man­aging that out­side the health care con­text is really dif­fi­cult for people.”

23andMe aims to al­le­vi­ate some of this dif­fi­culty by provid­ing in­ter­pret­a­tion for the res­ults. Their re­ports cite sci­entif­ic stud­ies and use a star sys­tem to in­dic­ate the level of cred­ib­il­ity. As new stud­ies come out, 23andMe sends an email in­cor­por­at­ing new in­form­a­tion to keep people en­gaged in their ge­net­ics.

But this is where the pace of ge­net­ics re­search gets tricky.

This isn’t a prob­lem with the sci­ent­ists and clini­cians at 23andMe. “What it comes down to,” Levy says, “is if we’re go­ing to live on the cut­ting edge of know­ledge, new dis­cov­er­ies are ac­ted on right away. The down­side is that new dis­cov­er­ies some­times make a mis­take.” 

Levy says he is more open to DTC ge­net­ic test­ing than most phys­i­cians; that it comes down to a philo­sophy of autonomy versus pa­ter­nal­ism, and he’s a fan of autonomy. Yet en­gage­ment re­lies on con­tin­ued par­ti­cip­a­tion and ac­count­ab­il­ity on the part of the con­sumer as well. Keep­ing up with the in­form­a­tion, Levy says, is equally the re­spons­ib­il­ity of the con­sumer and the ge­net­ics-in­ter­pret­a­tion com­pany. 

Levy does re­com­mend that con­sumers bring their res­ults to their doc­tor as well, something that 23andMe and many ge­net­ics pro­fes­sion­als en­cour­age, par­tic­u­larly if con­sumers are con­sid­er­ing a life­style or med­ic­al change based on their test res­ults. “[An in­di­vidu­al] could cause ser­i­ous per­man­ent harm to them­selves by mis­in­ter­pret­ing the in­form­a­tion they get,” Levy says.

Doc­tors and the Edu­ca­tion De­fi­cit

As of now though, stud­ies show that the ma­jor­ity of test con­sumers don’t share res­ults with their doc­tors. In fact, shar­ing the res­ults with a doc­tor has two sig­ni­fic­ant road­b­locks: cost and ex­per­i­ence. 

While the ac­tu­al DNA test­ing is quickly be­com­ing in­ex­pens­ive and ubi­quit­ous, pro­fes­sion­al in­ter­pret­a­tion still re­quires time and ex­pert­ise. This iron­ic­ally makes the phys­i­cian fol­low-up more of a lim­it­ing factor in un­der­stand­ing res­ults than the tests them­selves. 

The second prob­lem is that even doc­tors and spe­cial­ists in the field some­times don’t know or can’t keep up with ge­net­ics re­search. “There’s a sig­ni­fic­ant edu­ca­tion­al de­fi­cit — on the con­sumer and also the phys­i­cian side,” says Mi­chael Dougherty, dir­ect­or of edu­ca­tion at the Amer­ic­an So­ci­ety of Hu­man Ge­net­ics. “If you take [DTC res­ults] to the phys­i­cian, gen­er­ally they don’t know what to do with it.”

“There’s a sig­ni­fic­ant edu­ca­tion­al de­fi­cit.”

As a res­ult, med­ic­al groups are work­ing to in­crease edu­ca­tion of the pub­lic and of phys­i­cians re­gard­ing ge­net­ics and its grow­ing role in medi­cine. Dougherty ex­plains that while doc­tors should refer pa­tients to spe­cial­ists if they sus­pect the in­di­vidu­al has a ge­net­ic con­di­tion, ge­net­ic spe­cial­ists are un­for­tu­nately in short sup­ply. This makes it im­port­ant for phys­i­cians to be­come more fa­mil­i­ar with the field. “Where the greatest [edu­ca­tion­al] need ex­ists is with front­line health pro­viders — nurses phys­i­cians, primary-care phys­i­cians, nu­tri­tion­ists, et cet­era,” he says. “It will be­come in­cum­bent in­creas­ingly on primary-care phys­i­cians to re­cog­nize when the ge­net­ic test res­ults are mov­ing bey­ond area of their ex­pert­ise.” 

In ad­di­tion to edu­ca­tion pro­grams, data through DTC tests them­selves can also con­trib­ute to on­go­ing ge­net­ic re­search to help bet­ter un­der­stand res­ults. Ninety per­cent of 23andMe test con­sumers op­ted in to par­ti­cip­ate in the re­search, al­low­ing 23andMe sci­ent­ists to view their an­onym­ous data and identi­fy hun­dreds of new ge­net­ic as­so­ci­ations and identi­fy tar­gets for po­ten­tial new drugs and treat­ments.

The op­por­tun­ity to con­trib­ute to that re­search is one of the things 23andMe val­ues most. “I’d like to think that some treat­ment 20, 30, 40 years from now — I’d like to think my fam­ily par­ti­cip­ated in mak­ing some of those things avail­able,” Afar­i­an said.

As our con­ver­sa­tion was wrap­ping up, I asked if there was any­thing she’d like to add.

“Well it sounds like you’re not a cus­tom­er,” she said. “I would love to send you a kit!” 

I’m not sure I could handle the un­cer­tainty.

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