Multi-gene test may find risk for heart dis­ease and more

The Western Star - - OBITUARIES -

You know your choles­terol, your blood pres­sure ... your heart gene score? Researcher­s say a new way of an­a­lyz­ing ge­netic test data may one day help iden­tify peo­ple at high risk of a youth­ful heart at­tack in time to help.

To­day, gene test­ing mostly fo­cuses on rare mu­ta­tions in one or a few genes, like those that cause cys­tic fi­bro­sis or sickle cell dis­ease, or the BRCA gene re­spon­si­ble for a small frac­tion of breast can­cer. It is less use­ful for some of the most com­mon dis­eases, such as heart dis­ease or di­a­betes, be­cause they are in­flu­enced by vast num­bers of genes—gone—wrong work­ing to­gether in com­pli­cated ways.

Mon­day, researcher­s re­ported a new way to mea­sure mil­lions of small ge­netic vari­a­tions that add up to cause harm, let­ting them cal­cu­late some­one’s in­her­ited risk for the most com­mon form of heart dis­ease and four other se­ri­ous dis­or­ders. The po­ten­tial car­diac im­pact: They es­ti­mated that up to 25 mil­lion Amer­i­cans may have triple the av­er­age per­son’s risk for coronary artery dis­ease even if they haven’t yet de­vel­oped warn­ing signs like high choles­terol.

“What I fore­see is in five years, each per­son will know this risk num­ber, this ‘poly­genic risk score,’ sim­i­lar to the way each per­son knows his or her choles­terol,” said Dr. Sekar Kathire­san who led the re­search team from the Broad In­sti­tute, Mas­sachusetts Gen­eral Hos­pi­tal and Har­vard Med­i­cal School.

If the ap­proach pans out and doc­tors adopt it, a bad score wouldn’t mean you’d get a dis­ease, just that your ge­netic makeup in­creases the chance — one more piece of in­for­ma­tion in de­cid­ing care. For ex­am­ple, when the researcher­s tested the sys­tem us­ing a DNA data­base from Bri­tain, less than 1 per cent of peo­ple with the low­est risk scores were di­ag­nosed with coronary artery dis­ease, com­pared to 11 per cent of peo­ple with the high­est risk score.

“There are things you can do to lower the risk,” Kathire­san said — the usual ad­vice about diet, ex­er­cise, choles­terol med­i­ca­tion and not smok­ing helps.

On the flip side, a low—risk score “doesn’t give you a free pass,” he added. An un­healthy lifestyle could over­whelm the pro­tec­tion of good genes.

The scor­ing sys­tem also can pre­dict an in­creased risk of Type 2 di­a­betes, in­flam­ma­tory bowel dis­ease, breast can­cer and an ir­reg­u­lar heart­beat called atrial fib­ril­la­tion, the team re­ported in the jour­nal Na­ture Ge­net­ics — not­ing that next steps in­clude learn­ing what might like­wise lower those risks.

It doesn’t re­quire the most so­phis­ti­cated type of ge­netic test­ing. In­stead, Kathire­san can cal­cu­late risk scores for those five dis­eases — even­tu­ally maybe more — sim­ply by re­an­a­lyz­ing the kind of raw data peo­ple re­ceive af­ter send­ing a cheek swab to com­pa­nies like 23andMe.

A ge­neti­cist who spe­cial­izes in car­dio­vas­cu­lar dis­ease, he hopes to open a web­site where peo­ple can send in such data to learn their heart risk, as part of con­tin­u­ing re­search. Kathire­san and co—au­thor Dr. Amit Khera, a Mass Gen­eral car­di­ol­o­gist, are co—in­ven­tors on a patent ap­pli­ca­tion for the sys­tem.

Other sci­en­tists and com­pa­nies have long sought ways to mea­sure risk from mul­ti­ple, ad­di­tive gene ef­fects — the “poly” in poly­genic — and Myr­iad Ge­net­ics has be­gun sell­ing a type of poly­genic test for breast can­cer risk.

But spe­cial­ists in heart dis­ease and ge­net­ics who weren’t in­volved with the re­search called the new find­ings ex­cit­ing be­cause of their scope.

“The re­sults should be eye— open­ing for car­di­ol­o­gists,” said Dr. Charles C. Hong, direc­tor of car­dio­vas­cu­lar re­search at the Univer­sity of Mary­land School of Medicine. “The only dis­ap­point­ment is that this score ap­plies only to those with Euro­pean ances­try, so I won­der if sim­i­lar scores are in the works for the large ma­jor­ity of the world pop­u­la­tion that is not white.”

Hong pointed to a friend who re­cently died of a mas­sive heart at­tack de­spite be­ing a su­per— fit marathon run­ner who’d never smoked, the kind of puz­zling death that doc­tors have long hoped that a bet­ter un­der­stand­ing of ge­net­ics could help to pre­vent.

“Most of the vari­a­tion in dis­ease risk comes from an enor­mous num­ber of very tiny ef­fects” in genes, agreed Stan­ford Univer­sity ge­net­ics pro­fes­sor Jonathan Pritchard. “This is the first time poly­genic scores have re­ally been shown to reach the level of pre­ci­sion where they can have an im­pact” on pa­tient health.

First, the Bos­ton—based team combed pre­vi­ous stud­ies that mapped the DNA of large num­bers of peo­ple, look­ing for links to the five dis­eases — not out­right mu­ta­tions but mi­nor mis­spellings in the ge­netic code.

Each vari­a­tion alone would have only a tiny ef­fect on health. They de­vel­oped a com­put­er­ized sys­tem that an­a­lyzed how those ef­fects add up, and tested it us­ing DNA and med­i­cal records from 400,000 peo­ple stored in Bri­tain’s UK Biobank. Scores more than three times the av­er­age per­son’s risk were deemed high.

The As­so­ci­ated Press Health & Science Depart­ment re­ceives sup­port from the Howard Hughes Med­i­cal In­sti­tute’s Depart­ment of Science Ed­u­ca­tion. The AP is solely re­spon­si­ble for all con­tent.

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