Novel Alzheimer’s disease risk variants identified based on whole-genome sequencing of APOE ε4 carriers
Abstract 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 m...
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| Format: | Article |
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Nature Publishing Group
2021-05-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-021-01412-9 |
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| author | Jong-Ho Park Inho Park Emilia Moonkyung Youm Sejoon Lee June-Hee Park Jongan Lee Dong Young Lee Min Soo Byun Jun Ho Lee Dahyun Yi Sun Ju Chung Kye Won Park Nari Choi Seong Yoon Kim Woon Yoon Hoyoung An Ki woong Kim Seong Hye Choi Jee Hyang Jeong Eun-Joo Kim Hyojin Kang Junehawk Lee Younghoon Kim Eunjung Alice Lee Sang Won Seo Duk L. Na Jong-Won Kim |
| author_facet | Jong-Ho Park Inho Park Emilia Moonkyung Youm Sejoon Lee June-Hee Park Jongan Lee Dong Young Lee Min Soo Byun Jun Ho Lee Dahyun Yi Sun Ju Chung Kye Won Park Nari Choi Seong Yoon Kim Woon Yoon Hoyoung An Ki woong Kim Seong Hye Choi Jee Hyang Jeong Eun-Joo Kim Hyojin Kang Junehawk Lee Younghoon Kim Eunjung Alice Lee Sang Won Seo Duk L. Na Jong-Won Kim |
| author_sort | Jong-Ho Park |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-b686f6f15ea94d038d880b7bca899d2a |
| institution | Kabale University |
| issn | 2158-3188 |
| language | English |
| publishDate | 2021-05-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj-art-b686f6f15ea94d038d880b7bca899d2a2025-08-20T03:53:46ZengNature Publishing GroupTranslational Psychiatry2158-31882021-05-0111111210.1038/s41398-021-01412-9Novel Alzheimer’s disease risk variants identified based on whole-genome sequencing of APOE ε4 carriersJong-Ho Park0Inho Park1Emilia Moonkyung Youm2Sejoon Lee3June-Hee Park4Jongan Lee5Dong Young Lee6Min Soo Byun7Jun Ho Lee8Dahyun Yi9Sun Ju Chung10Kye Won Park11Nari Choi12Seong Yoon Kim13Woon Yoon14Hoyoung An15Ki woong Kim16Seong Hye Choi17Jee Hyang Jeong18Eun-Joo Kim19Hyojin Kang20Junehawk Lee21Younghoon Kim22Eunjung Alice Lee23Sang Won Seo24Duk L. Na25Jong-Won Kim26Clinical Genomics Center, Samsung Medical CenterCenter for Precision Medicine, Gangnam Severance Hospital, Yonsei University College of MedicineDepartment of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Samsung Medical CenterPrecision Medicine Center, Seoul National University Bundang HospitalResearch Institute for Future Medicine, Samsung Medical CenterSubtropical Livestock Research Institute, National Institute of Animal Science, RDADepartment of Neuropsychiatry, Seoul National University Hospital & Department of Psychiatry, Seoul National University College of MedicineDepartment of Neuropsychiatry, Seoul National University Bundang HospitalDepartment of Psychiatry, National Center for Mental HealthInstitute of Human Behavioral Medicine, Medical Research Center Seoul National UniversityDepartment of Neurology, Asan Medical Center, University of Ulsan College of MedicineDepartment of Neurology, Asan Medical Center, University of Ulsan College of MedicineDepartment of Neurology, Asan Medical Center, University of Ulsan College of MedicineDepartment of Psychiatry, Asan Medical Center, University of Ulsan College of MedicineDepartment of Psychiatry, Asan Medical Center, University of Ulsan College of MedicineDepartment of Neuropsychiatry, St. Andrew’s HospitalDepartment of Neuropsychiatry, Seoul National University Bundang HospitalDepartment of Neurology, Inha University School of MedicineDepartment of Neurology, Ewha Womans University Seoul Hospital, Ewha Womans University School of MedicineDepartment of Neurology, Pusan National University Hospital and Biomedical Research Institute, Pusan National University School of MedicineDivision of Supercomputing, KISTIDivision of Supercomputing, KISTIDivision of Supercomputing, KISTIDivision of Genetics and Genomics, Boston Children’s Hospital, Harvard Medical SchoolDepartment of Neurology, Sungkyunkwan University School of Medicine and Neuroscience Center, Samsung Medical CenterDepartment of Neurology, Sungkyunkwan University School of Medicine and Neuroscience Center, Samsung Medical CenterClinical Genomics Center, Samsung Medical CenterAbstract 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.https://doi.org/10.1038/s41398-021-01412-9 |
| spellingShingle | Jong-Ho Park Inho Park Emilia Moonkyung Youm Sejoon Lee June-Hee Park Jongan Lee Dong Young Lee Min Soo Byun Jun Ho Lee Dahyun Yi Sun Ju Chung Kye Won Park Nari Choi Seong Yoon Kim Woon Yoon Hoyoung An Ki woong Kim Seong Hye Choi Jee Hyang Jeong Eun-Joo Kim Hyojin Kang Junehawk Lee Younghoon Kim Eunjung Alice Lee Sang Won Seo Duk L. Na Jong-Won Kim Novel Alzheimer’s disease risk variants identified based on whole-genome sequencing of APOE ε4 carriers Translational Psychiatry |
| title | Novel Alzheimer’s disease risk variants identified based on whole-genome sequencing of APOE ε4 carriers |
| title_full | Novel Alzheimer’s disease risk variants identified based on whole-genome sequencing of APOE ε4 carriers |
| title_fullStr | Novel Alzheimer’s disease risk variants identified based on whole-genome sequencing of APOE ε4 carriers |
| title_full_unstemmed | Novel Alzheimer’s disease risk variants identified based on whole-genome sequencing of APOE ε4 carriers |
| title_short | Novel Alzheimer’s disease risk variants identified based on whole-genome sequencing of APOE ε4 carriers |
| title_sort | novel alzheimer s disease risk variants identified based on whole genome sequencing of apoe ε4 carriers |
| url | https://doi.org/10.1038/s41398-021-01412-9 |
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