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Review
. 2020 Aug:142:104953.
doi: 10.1016/j.nbd.2020.104953. Epub 2020 May 20.

Polygenic risk and pleiotropy in neurodegenerative diseases

Eftychia Bellou  1 , Joshua Stevenson-Hoare  1 , Valentina Escott-Price  2
Affiliations
Review

Polygenic risk and pleiotropy in neurodegenerative diseases

Eftychia Bellou et al. Neurobiol Dis. 2020 Aug.

Abstract

In this paper we explore the phenomenon of pleiotropy in neurodegenerative diseases, focusing on Alzheimer's disease (AD). We summarize the various techniques developed to investigate pleiotropy among traits, elaborating in the polygenic risk scores (PRS) analysis. PRS was designed to assess a cumulative effect of a large number of SNPs for association with a disease and, later for disease risk prediction. Since genetic predictions rely on heritability, we discuss SNP-based heritability from genome-wide association studies and its contribution to the prediction accuracy of PRS. We review work examining pleiotropy in neurodegenerative diseases and related phenotypes and biomarkers. We conclude that the exploitation of pleiotropy may aid in the identification of novel genes and provide further insights in the disease mechanisms, and along with PRS analysis, may be advantageous for precision medicine.

Keywords: Heritability; Neurodegenerative disease; Pleiotropy; Polygenic risk score.

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Conflict of interest statement

Declaration of Competing Interest The authors EB, VEP have collaborated with Cytox Ltd. through their InnovateUK grant funding.

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