Complex genetic susceptibility to vascular dementia and an evidence for its underlying genetic factors associated with memory and associative learning
Abstract
Genetic basis for vascular dementia (VD) as a typical complex disease has been limitedly reported from association studies conducted with candidate genes. Even recent genomewide association studies (GWAS) could hardly identify additional genetic factors for VD. Although a considerable complexity for its genetic architecture was suspected, there were some challenges to identify false negative associations that resulted from the GWAS. Challenges to identifying genetic factors and their functions after the trials of GWAS revealed that splicing of primary transcript was inhibited (SYK) or delayed (PHLDB2) by a nucleotide substitution of the corresponding gene. The studies gave us the lesson that integrated investigations with statistical genomics as well as functional genomics are needed to identify false negatives from the GWAS. Such endeavors would provide key insights into aspects of underlying nucleotide architectures of VD and incorporate the genetic factors into clinical practice. The recent genetic association studies for susceptibility to VD were briefly overviewed in this article. We also showed a challenge to understanding genetic dissection of VD by a genomic region enrichment analysis with distal cis-regulatory sequences. The analysis with a variant set of potential false negatives from the GWAS revealed that the variants were significantly enriched near genes involved in critical biological processes to VD.
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GWAS of vascular dementia show a small effect of SNPs at the androgen receptor gene locus, a finding not observed in all ethnic groups.
“GWAS of vascular dementia have shown small effect of SNPs in the androgen receptor gene locus (Schrijvers et al., 2012), a finding not observed in all ethnic groups (Lee and Kim, 2013).”
From The Pathobiology of Vascular Dementia (2013) · cites this paper as Lee and Kim, 2013
A strong link between ApoE and sporadic vascular cognitive impairment has not been established.
“Nevertheless, a strong link between ApoE and sporadic VCI has not been established (Lee and Kim, 2013; Yu et al., 2013).”
From The Pathobiology of Vascular Dementia (2013) · cites this paper as Lee and Kim, 2013
Linkage studies in patients with MRI white matter lesions discovered several loci, but no specific gene has been identified and the findings await replication and validation.
“Linkage studies in patients with white matter lesions on MRI have discovered several loci (Schmidt et al., 2012), but no specific gene has been identified and the findings await replication and validation (Lee and Kim, 2013; Markus, 2008).”
From The Pathobiology of Vascular Dementia (2013) · cites this paper as Lee and Kim, 2013
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- Authors
- Lee, C., & Kim, Y.
- Affiliations
- Soongsil University (KR)
- Corresponding author
- Lee, Chaeyoung
- ORCID
- Lee, Chaeyoung
- Venue
- Gene
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 516
- Issue
- 1
- Pages
- 152-157
- ISSN
- 0378-1119 (ISSN-L)
- OpenAlex
- W1994973352
- Cited by
- 12
- References
- 49
- Citations by year
- 2026: 1 · 2024: 2 · 2022: 1 · 2017: 1 · 2016: 4 · 2015: 2 · 2013: 1
- FWCI
- 0.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gene (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Science and Technology (2012R1A1B3002096)
- National Research Foundation of Korea
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- vascular dementia, genetic susceptibility, complex diseases, genetic architecture, Syk, alternative splicing, memory, associative learning
- MeSH terms
- Genotype, Humans, Memory, Dementia, Vascular, Genome, Human, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genomics, Genome-Wide Association Study
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