Can at-home genetic tests improve rare diagnosis?

Of all the inno­va­tions issu­ing from Sil­i­con Val­ley and trans­form­ing our lives, few have the poten­tial to impact us quite so rad­i­cal­ly as at-home genet­ic test­ing of our DNA.

For just a one-off fee and a swab of your sali­va, com­pa­nies such as 23andMe will reveal your pre­dis­po­si­tion to a grow­ing num­ber of dis­eases, includ­ing breast can­cer, Alzheimer’s, Parkinson’s and type‑2 dia­betes, along with car­ri­er sta­tus for con­di­tions such as cys­tic fibro­sis.

But while com­mon, com­plex dis­or­ders are increas­ing­ly well served in this brave new world, there are con­cerns about the lack of empha­sis on rare dis­eases.

Are rare disease diagnoses too expensive?

A recent study by Impe­r­i­al Col­lege Health Part­ners (ICHP) reveals the lengthy process of diag­nos­ing rare dis­eases has cost NHS Eng­land £3.4 bil­lion in the last decade.

“The costs stat­ed in our report are drawn from analysing the Hos­pi­tal Episode Sta­tis­tics NHS Dig­i­tal data­base of over 60 mil­lion patients,” explains Julia Wilkins, head of data and ana­lyt­ics at ICHP. “The research focused on hos­pi­tal vis­its and activ­i­ty in the lead up to diag­no­sis over the pri­or ten years, with an analy­sis of the data find­ing a high­er num­ber of hos­pi­tal vis­its and accom­pa­ny­ing costs per rare dis­ease patient when com­pared to the gen­er­al patient pop­u­la­tion.”

There are the begin­nings of offer­ings in the direct con­sumer space around whole genomes and exomes, but there’s still a lot to learn about how to inter­pret that data

But these fig­ures only tell us part of the sto­ry, accord­ing to Nick Meade, direc­tor of pol­i­cy at Genet­ic Alliance UK. “£3.4 bil­lion is prob­a­bly a vast under­es­ti­ma­tion of the impact on the state more broad­ly,” he says.

If the suf­fer­er from a rare dis­ease can’t work, he or she will no longer pay tax­es, will prob­a­bly need to draw some form of state secu­ri­ty, as well as cop­ing with the mas­sive cost to their own qual­i­ty of life.

“The clas­sic exam­ple would be if you can deliv­er mus­cu­lar dys­tro­phy treat­ment when peo­ple can still walk then you’ll be able to stop them from hav­ing to use a wheel­chair,” says Mr Meade.

At-home genetic testing will revolutionise diagnosis

Last year, the Genet­ic Alliance pro­duced a study in col­lab­o­ra­tion with Birm­ing­ham Children’s Hos­pi­tal which con­cen­trat­ed on the undi­ag­nosed com­mu­ni­ty who suf­fer, he adds, from “a sub­set of rare con­di­tions that are so rare they’re not that well under­stood and genet­ic tests won’t diag­nose them because they just haven’t been defined prop­er­ly yet”. The scale of the prob­lem, par­tic­u­lar­ly with very ill chil­dren, is huge.

At present, at-home genet­ic test­ing indi­cates around ten health pre­dis­po­si­tions, as well as detail­ing car­ri­er sta­tus, for as many as forty con­di­tions and trait reports for even things such as freck­les, red hair, bald spots, ice cream flavour pref­er­ence and mos­qui­to bite fre­quen­cy. This makes it all seem like a bit of fun; the lat­est fad you can indulge in after hav­ing uploaded all your hol­i­day pho­tos to Insta­gram and arrived home a lot quick­er after down­load­ing Uber. But when it comes to get­ting our own DNA test­ed, most of us are enter­ing a realm we do not under­stand.

So can 23andMe, for exam­ple, help the NHS diag­nose rare dis­eases? “One of the ben­e­fits of 23andMe is to act as a broad screen to iden­ti­fy genet­ic health risks that peo­ple might be unaware of, espe­cial­ly for those who do not qual­i­fy for clin­i­cal test­ing. Our Health + Ances­try ser­vice does report on var­i­ous rare dis­eases, for exam­ple, MUTYH-asso­ci­at­ed poly­po­sis [genet­ic risk for a spe­cif­ic col­orec­tal can­cer syn­drome] and hered­i­tary hemochro­mato­sis [HFE-relat­ed genet­ic risk for iron over­load],” the com­pa­ny says.

Consumer genetic data used to aid prevention

This can, of course, have far-reach­ing con­se­quences for those who use such ser­vices and receive wor­ry­ing results. As the com­pa­ny explains: “We’ve seen many cas­es of cus­tomers learn­ing of genet­ic risks for cer­tain con­di­tions and dis­cussing those results with their health­care providers, which has led to fol­low-up test­ing and pre­ven­ta­tive mea­sures being tak­en.

“Our goal is to con­tin­ue encour­ag­ing peo­ple to take a proac­tive stance to their health, using our reports as a prompt to ini­ti­ate con­ver­sa­tions with their health­care provider.”

If at-home genet­ic test­ing reveals some­thing that looks wor­ry­ing, the next step is to go to the doc­tor who, if also con­cerned, will order a fresh test through the NHS.

Pro­fes­sor Sir Mark Caulfield, inter­im chief exec­u­tive and chief sci­en­tist at Genomics Eng­land, explains: “At the present time, direct con­sumer test­ing, offered by 23andMe and oth­ers, pre­dom­i­nant­ly uses analy­sis based on geno­typ­ing. There are the begin­nings of offer­ings in the direct con­sumer space around whole genomes and exomes, but there’s still a lot to learn about how to inter­pret that data.

“My view is peo­ple should be free to choose what they do and we know about 175,000 UK cit­i­zens have done a 23andMe test, so there’s an appetite and curios­i­ty out there. What we need is to make as much genomics usable in the health sys­tem so we can ben­e­fit peo­ple.”

Genetic testing in the future

But Sir Mark is con­cerned about “implic­it inequity” when it comes to at-home genet­ic test­ing in future. Yes, an ever-increas­ing num­ber of peo­ple will be able to afford to send off DNA sam­ples and decode their genet­ic infor­ma­tion pri­vate­ly, but what about those who can’t afford it? That’s why bod­ies such as Genomics Eng­land are so focused on incor­po­rat­ing genom­ic med­i­cine into the NHS.

This is some­thing that has made the UK a world leader in genom­ic med­i­cine. Even at-home genet­ic test­ing com­pa­nies such as 23andMe have noticed. Their spokesman adds: “We know genet­ic test­ing and genome sequenc­ing for dis­ease diag­no­sis and pre­ven­tion is cur­rent­ly high on the agen­da in the UK, for exam­ple with the 100,000 Genomes Project and the renewed bid to sequence five mil­lion genomes in the next five years.”

To iden­ti­fy rare dis­eases as ear­ly as pos­si­ble and make sure they are treat­ed, Sir Mark hopes the NHS will even­tu­al­ly offer a genet­ic test at birth.

“What might you find in ear­ly life if you use the whole genome?” he asks, explain­ing that a test could be con­duct­ed by tak­ing a DNA sam­ple from a baby’s umbil­i­cal cord.

How­ev­er genet­ic test­ing is con­duct­ed in the future, it seems cer­tain the results will have not just a trans­for­ma­tive impact on how we think about our health, but could sig­nif­i­cant­ly reduce the cost bur­den of rare dis­eases on the NHS.