Genetic assessment of age-associated Alzheimer disease risk: Development and validation of a polygenic hazard score.
Rahul S DesikanChun-Chieh FanYunpeng WangAndrew J SchorkHoward J CabralL Adrienne CupplesWesley K ThompsonLilah BesserWalter A KukullDominic HollandChi-Hua ChenJames B BrewerDavid S KarowKarolina KauppiAree WitoelarCeleste M KarchLuke W BonhamJennifer S YokoyamaHoward J RosenBruce L MillerWilliam P DillonDavid M WilsonChristopher P HessMargaret Pericak-VanceJonathan L HainesLindsay A FarrerRichard MayeuxJohn HardyAlison M GoateBradley T HymanGerard D SchellenbergLinda K McEvoyOle A AndreassenAnders M DalePublished in: PLoS medicine (2017)
We have developed a PHS for quantifying individual differences in age-specific genetic risk for AD. Within the cohorts studied here, polygenic architecture plays an important role in modifying AD risk beyond APOE. With thorough validation, quantification of inherited genetic variation may prove useful for stratifying AD risk and as an enrichment strategy in therapeutic trials.