Whole Genome Variable Number Tandem Repeat Analysis in Alzheimer Disease.

IF 3 3区医学 Q2 CLINICAL NEUROLOGY

Neurology-Genetics Pub Date : 2025-02-14 eCollection Date: 2025-04-01 DOI:10.1212/NXG.0000000000200241

Alesha Heath, M Windy McNerney, Jerome Yesavage

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引用次数: 0

Abstract

Background and objectives: Investigation into different allelic variants may yield new associative genes to predict late-onset Alzheimer disease (LOAD). Variable number tandem repeats (VNTRs) are important polymorphic components of the genome; however, they have been previously overlooked because of their complex genotyping. New software can now determine differing lengths of VNTRs; however, this has not been tested in a large case-control population.

Methods: We used VNTRseek to genotype over 200,000 tandem repeats in 9,501 cases and controls from the Alzheimer's Disease Sequencing Project. We first identified limiting factors of this analysis and then examined the association of VNTRs with AD diagnosis in a subset of non-Hispanic White participants.

Results: We found that VNTRs were highly associated with areas of the genome with a high number of previously identified variants. From our case-control analysis, we identified 9 VNTRs with a repeat allele length associated with LOAD including VNTRs on DSC3, NR2E3, CCNY, PKP4, GRAP, and MAP6.

Discussion: We were able to show the feasibility of this new type of analysis in large-scale whole-genome sequencing data and identify promising VNTRs that are associated with LOAD.

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来源期刊

Neurology-Genetics Medicine-Neurology (clinical)

CiteScore

6.30

自引率

3.20%

发文量

107

审稿时长

15 weeks

期刊介绍： Neurology: Genetics is an online open access journal publishing peer-reviewed reports in the field of neurogenetics. Original articles in all areas of neurogenetics will be published including rare and common genetic variation, genotype-phenotype correlations, outlier phenotypes as a result of mutations in known disease-genes, and genetic variations with a putative link to diseases. This will include studies reporting on genetic disease risk and pharmacogenomics. In addition, Neurology: Genetics will publish results of gene-based clinical trials (viral, ASO, etc.). Genetically engineered model systems are not a primary focus of Neurology: Genetics, but studies using model systems for treatment trials are welcome, including well-powered studies reporting negative results.