The Multifaceted Influence of Genetic Ancestry on Neurodegenerative Diseases

Published on October 20, 2022

It’s like studying different paintings to understand the art world. Genomic research has given us incredible insights into the complex genetics behind neurodegenerative diseases. However, most studies have focused on individuals of European ancestry, leaving out important information from other populations. Recent studies have shown that genetic variations have varying effects on disease risk and presentation in non-European populations. This emphasizes the crucial role of ancestry in predicting disease risk and unraveling the biological mechanisms of neurodegeneration. In this review, we explore the impact of two essential genetic regions, 17q21.31 and APOE, on neurodegenerative disease risk in non-European populations. We also touch upon global population differences and evolutionary genetics to better understand these disparities. To bridge the gap in knowledge, it is imperative to include more individuals with non-European ancestry in genome-wide association studies (GWAS) and biomarker analyses. By doing so, we can fill existing gaps and better comprehend the risk, diagnosis, and treatment of neurodegenerative diseases across diverse populations.

Advances in genomic research over the last two decades have greatly enhanced our knowledge concerning the genetic landscape and pathophysiological processes involved in multiple neurodegenerative diseases. However, current insights arise almost exclusively from studies on individuals of European ancestry. Despite this, studies have revealed that genetic variation differentially impacts risk for, and clinical presentation of neurodegenerative disease in non-European populations, conveying the importance of ancestry in predicting disease risk and understanding the biological mechanisms contributing to neurodegeneration. We review the genetic influence of two important disease-associated loci, 17q21.31 (the “MAPT locus”) and APOE, to neurodegenerative disease risk in non-European populations, touching on global population differences and evolutionary genetics by ancestry that may underlie some of these differences. We conclude there is a need to increase representation of non-European ancestry individuals in genome-wide association studies (GWAS) and biomarker analyses in order to help resolve existing disparities in understanding risk for, diagnosis of, and treatment for neurodegenerative diseases in diverse populations.

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