Novel Alzheimer’s disease risk variants identified based on whole-genome sequencing of APOE ε4 carriers
| Autor: | Dong Young Lee, Eun-Joo Kim, Seong Yoon Kim, Nari Choi, Dahyun Yi, Duk L. Na, Jee Hyang Jeong, Hyojin Kang, J. H. Park, Sang Won Seo, Jongan Lee, Inho Park, Ki Woong Kim, Jong-Ho Park, Junehawk Lee, Eunjung Lee, Min Soo Byun, Seong Hye Choi, Kye Won Park, Sun Ju Chung, Younghoon Kim, Jong-Won Kim, Sejoon Lee, Emilia Moonkyung Youm, Woon Yoon, Jun Ho Lee, Hoyoung An |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Apolipoprotein E Genotype Apolipoprotein E4 Neurosciences. Biological psychiatry. Neuropsychiatry Genome-wide association study Single-nucleotide polymorphism Disease Biology Article 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Apolipoproteins E Alzheimer Disease Humans Clinical genetics Allele Gene Biological Psychiatry Alleles Genetic association Aged Genetics Whole genome sequencing Comparative genomics Neurodegenerative Diseases Psychiatry and Mental health 030104 developmental biology 030217 neurology & neurosurgery RC321-571 Genome-Wide Association Study |
| Zdroj: | Translational Psychiatry Translational Psychiatry, Vol 11, Iss 1, Pp 1-12 (2021) |
| ISSN: | 2158-3188 |
| Popis: | Alzheimer’s disease (AD) is a progressive neurodegenerative disease associated with a complex genetic etiology. Besides the apolipoprotein E ε4 (APOE ε4) allele, a few dozen other genetic loci associated with AD have been identified through genome-wide association studies (GWAS) conducted mainly in individuals of European ancestry. Recently, several GWAS performed in other ethnic groups have shown the importance of replicating studies that identify previously established risk loci and searching for novel risk loci. APOE-stratified GWAS have yielded novel AD risk loci that might be masked by, or be dependent on, APOE alleles. We performed whole-genome sequencing (WGS) on DNA from blood samples of 331 AD patients and 169 elderly controls of Korean ethnicity who were APOE ε4 carriers. Based on WGS data, we designed a customized AD chip (cAD chip) for further analysis on an independent set of 543 AD patients and 894 elderly controls of the same ethnicity, regardless of their APOE ε4 allele status. Combined analysis of WGS and cAD chip data revealed that SNPs rs1890078 (P = 6.64E−07) and rs12594991 (P = 2.03E−07) in SORCS1 and CHD2 genes, respectively, are novel genetic variants among APOE ε4 carriers in the Korean population. In addition, nine possible novel variants that were rare in individuals of European ancestry but common in East Asia were identified. This study demonstrates that APOE-stratified analysis is important for understanding the genetic background of AD in different populations. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|