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Genetic Risk for Disease
The field of genetics continues to evolve as we begin to understand how different genes affect risk for disease, including Alzheimer’s disease.
Genetics is the study of how different characteristics and predispositions are passed on through DNA. DNA is shaped in a double helix with a phosphate backbone and rungs made of nucleotide bases, of which there are four possibilities: Adenine (A), Cytosine (C), Guanine (G), and Thymine (T). The order of these nucleotide bases determines the genes that are expressed and the traits that you have.
While humans share 99.9% of the same genetic code, it is the 0.1% that is different that causes differences between humans in traits, disease risk, and other genetic predispositions. The different nucleotide bases arrangements are called “single nucleotide polymorphisms” or “SNPs,” which determine your genetic makeup known as your genotype.
It is now known that Alzheimer’s disease (AD) is caused by both modifiable (such as nutrition, exercise, sleep, etc.) and non-modifiable (genetics, age, gender at birth) risk factors.
It’s estimated that genetic factors make up 50-80% of AD risk, with Apolipoprotein E (ApoE) SNPs accounting for approximately 25% of this genetic risk. Recent studies have identified over 50 additional SNPs that contribute to AD risk.
However, most research studies clinical tests only utilize ApoE genetic risk, leaving gaps in the understanding of the full genetic risk for AD.
In “GenoRisk: A Polygenic Risk Score for Alzheimer’s Disease,” the authors used data from 4 independent genetic studies of AD to predict genetic risk for AD using different statistical prediction models. These models were then compared to determine the model that best predicted AD risk, resulting in a model that utilized 29 SNPs in addition to ApoE. The resulting score was termed “GenoRisk.”
The GenoRisk score was then adjusted for age and gender at birth to further personalize AD risk prediction. The resulting scores take genetic prediction for AD beyond the limited basic ApoE model.
The GenoRisk polygenic risk score shows that there is a range of risk within a given ApoE genotype. In some cases, individuals with a low-risk ApoE genotype may actually have a higher overall genetic risk than someone with a higher-risk ApoE genotype, and vice versa.
With a better understanding of how genes interact to affect AD risk, it is the hope that the GenoRisk score, which moves above and beyond ApoE alone, will be used to improve personalized treatment interventions and prevention and improve clinical trials.
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