2022.06.09
Genetics of Alzheimer's disease: an East Asian perspective
J Hum Genet. 2022 Jun 1. doi: 10.1038/s10038-022-01050-z. Online ahead of print.
Miyashita A1,4, Kikuchi M2,3,4, Hara N1,4, Ikeuchi T1
1Department of Molecular Genetics, Brain Research Institute, Niigata University
2Department of Genome Informatics, Graduate School of Medicine, Osaka University
3Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo
4These authors contributed equally.
Abstract
Alzheimer's disease (AD) is an age-related multifactorial neurodegenerative disorder. Advances in genome technology, including next generation sequencing have uncovered complex genetic effects in AD by analyzing both common and rare functional variants. Multiple lines of evidence suggest that the pathogenesis of AD is influenced by multiple genetic components rather than single genetic factor. Previous genetic studies on AD have predominantly included European ancestry cohorts; hence, the non-European population may be underrepresented, potentially leading to reduced diversity in AD genetic research. Additionally, ethnic diversity may result in dissimilar effects of genetic determinants in AD. APOE genotypes are a well-established genetic risk factor in AD, with the East Asian population having a higher risk of AD associated with the APOE ε4 allele. To date, seven genome-wide association studies (GWAS) have been conducted in East Asians, which report a total of 26 AD-associated loci. Several rare variants, including the p.H157Y variant in TREM2, and the p.G186R and p.R274W variants in SHARPIN are associated with risk of AD in East Asians. Extending genetic studies to diverse populations, including East Asians is necessary, which could yield more comprehensive insights into AD, and here we review the recent findings regarding the genetic determinants of AD from an East Asian perspective.
*Reprinted under the terms of the Creative Commons Attribution License (CC BY).
