How understudied populations leverage our understanding of Alzheimer’s disease genetics

Authors: Nadia Dehghani, Jose Bras, Rita Guerreiro

Published: 2020-12-07

Abstract

AbstractBackgroundThe majority of genome‐wide association studies have been conducted using samples with a European genetic background. As a field, we acknowledge this limitation and the need to increase the diversity of populations studied. A major challenge when designing and conducting such studies is to assimilate large samples sizes to have enough statistical power to detect variants associated with disease, particularly when trying to identify variants with low and rare minor allele frequencies. In this study, we aimed to illustrate the benefits, to genetic characterization of Alzheimer’s disease (AD), in researching currently understudied populations. This is important for both fair representation of world populations and the translatability of findings.MethodWe have conducted a thorough literature search to understand the contributions of studies, on different populations, to AD genetics.ResultTo accomplish this, we have systematically quantified the number of studies identifying mutations in known disease‐causing genes, in all countries across the world, and discussed the contributions of research in understudied populations to the identification of novel genetic factors in this disease. Related to this, we compared the varied effects of genome‐wide significant SNPs across populations by focusing on loci that show different association profiles between populations (a key example being APOE).ConclusionThis work functions to both highlight how understudied populations have furthered our understanding of AD genetics, and to help us gage our progress on understanding the genetic architecture of this disease in all populations.