Journal article
Transcript variants of genes involved in neurodegeneration are differentially regulated by the APOE and MAPT haplotypes
Genes, Vol.12(3), Article 423
2021
Abstract
Genetic variations at the Apolipoprotein E (ApoE) and microtubule-associated protein tau (MAPT) loci have been implicated in multiple neurogenerative diseases, but their exact molecular mechanisms are unclear. In this study, we performed transcript level linear modelling using the blood whole transcriptome data and genotypes of the 570 subjects in the Parkinson’s Progression Markers Initiative (PPMI) cohort. ApoE, MAPT haplotypes and two SNPs at the SNCA locus (rs356181, rs3910105) were used to detect expression quantitative trait loci eQTLs associated with the transcriptome and differential usage of transcript isoforms. As a result, we identified 151 genes associated with the genotypic variations, 29 cis and 122 trans eQTL positions. Profound effect with genome-wide significance of ApoE e4 haplotype on the expression of TOMM40 transcripts was identified. This finding potentially explains in part the frequently established genetic association with the APOE e4 haplotypes in neurodegenerative diseases. Moreover, MAPT haplotypes had significant differential impact on 23 transcripts from the 17q21.31 and 17q24.1 loci. MAPT haplotypes had also the largest up-regulating (256) and the largest down-regulating (−178) effect sizes measured as β values on two different transcripts from the same gene (LRRC37A2). Intronic SNP in the SNCA gene, rs3910105, differentially induced expression of three SNCA isoforms. In conclusion, this study established clear association between well-known haplotypic variance and transcript specific regulation in the blood. APOE e4 and MAPT H1/H2 haplotypic variants are associated with the expression of several genes related to the neurodegeneration.
Details
- Title
- Transcript variants of genes involved in neurodegeneration are differentially regulated by the APOE and MAPT haplotypes
- Authors/Creators
- S. Kõks (Author/Creator) - Perron Institute for Neurological and Translational ScienceA.L. Pfaff (Author/Creator) - Murdoch UniversityV.J. Bubb (Author/Creator) - University of LiverpoolJ.P. Quinn (Author/Creator) - University of Liverpool
- Publication Details
- Genes, Vol.12(3), Article 423
- Publisher
- MDPI
- Identifiers
- 991005544225507891
- Copyright
- © 2021 by the authors
- Murdoch Affiliation
- Centre for Molecular Medicine and Innovative Therapeutics
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.52 Neurodegenerative Diseases
- 1.52.57 Alzheimer's Mechanisms
- Web Of Science research areas
- Genetics & Heredity
- ESI research areas
- Molecular Biology & Genetics