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Polygenic risk scores predict Alzheimer disease risk

Recent findings indicated utility of polygenic hazard scores for determining individual differences in age-specific genetic risk for Alzheimer disease.

“We combined genetic data from large, independent cohorts of patients with [Alzheimer disease] with epidemiological estimates to create the scoring, then replicated our findings on an independent sample and validated them with known biomarkers of Alzheimer’s pathology,” Rahul S. Desikan, MD, PhD, of the University of California, San Francisco, said in a press release. “For any given individual, for a given age and genetic information, we can calculate your ‘personalized’ annualized risk for developing [Alzheimer disease]. That is, if you don’t already have dementia, what is your yearly risk for [Alzheimer disease] onset, based on your age and genetic information. We think these measures of polygenetic risk, of involving multiple genes, will be very informative for early [Alzheimer disease] diagnosis, both in determining prognosis and as an enrichment strategy in clinical trials.”

To identify single nucleotide polymorphisms associated with Alzheimer disease, researchers used genotype data from 17,008 individuals with Alzheimer disease and 37,154 controls. They then integrated the single nucleotide polymorphisms into a Cox proportional hazard model using genotype data from a subset of 6,409 individuals with Alzheimer disease and 9,386 older controls to provide polygenic hazard scores.

Individuals in the highest polygenic hazard score quartile developed Alzheimer disease at a significantly lower age and had the highest yearly Alzheimer disease incidence rate.

Anders Dale

Among participants with APOE 3/3, polygenic hazard scores modified the expected age of Alzheimer disease onset.

In independent cohorts, polygenic hazard scores strongly predicted empirical age of Alzheimer disease onset and progression from normal aging to Alzheimer disease.

“From a clinical perspective, the polygenic hazard score provides a novel way not just to assess an individual’s lifetime risk of developing [Alzheimer disease], but also to predict the age of disease onset,” Anders Dale, PhD, of the University of California, San Diego, said in the release. “Equally important, continuous polygenic testing of [Alzheimer disease] genetic risk can better inform prevention and therapeutic trials and be useful in determining which individuals are most likely to respond to therapy.” – by Amanda Oldt

Disclosure: Desikan reports no relevant financial disclosures. Please see the study for a full list of relevant financial disclosures.