Converging evidence for differential regulatory control of APOEε4 on African versus European haplotypes
Nuytemans, K.; LipkinVasquez, M.; Wang, L.; Van Booven, D.; Griswold, A. J.; Rajabli, F.; Celis, K.; Oron, O.; Hofmann, N.; Rolati, S.; Garcia-Serje, C.; Zhang, S.; Jin, F.; Argenziano, M.; Grant, S. F.; Chesi, A.; Brown, C. D.; Young, J. I.; Dykxhoorn, D. M.; Pericak-Vance, M. A.; Vance, J. M.
Show abstract
INTRODUCTIONThe difference in APOE{varepsilon}4 risk for Alzheimer disease (AD) between different populations is associated with APOE{varepsilon}4 local ancestry (LA). We examined LA SNPs with significant frequency differences between African and European/Japanese APOE{varepsilon}4 haplotypes for areas of differential regulation. METHODSWe performed two enhancer Massively Parallel Reporter Assay (MPRA) approaches, supplemented with single fragment reporter assays. We utilized Capture C analyses to support interactions with the APOE promoter. RESULTSThe TOMM40 intron 2 and 3 region showed increased enhancer activity in the European/Japanese versus African LA haplotypes in astrocytes and microglia. This region overlaps with APOE promoter interactions as assessed by Capture C analysis. Single variant analyses pinpoints rs2075650/rs157581, and rs59007384 as functionally different on these haplotypes. DISCUSSIONBoth differential regulatory function and Capture C data support an intronic region in TOMM40 as contributing to the differential APOE expression between African and European/Japanese LA.
Matching journals
The top 9 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Manifestations of genetic risk for Alzheimer's Disease in the blood: a cross-sectional multi-omic analysis in healthy adults aged 18-90+ 95%
- Co-localized SNPs Affecting the Expression of Taste Perception Genes are linked to Alzheimer's Disease 95%
- Modeling of mitochondrial genetic polymorphisms reveals induction of heteroplasmy by pleiotropic disease locus MT:10398A>G 93%
Similar papers in this journal
- Accurate DNA Methylation Predictor for C9orf72 Repeat Expansion Alleles in the Pathogenic Range 95%
- The genetic architecture of Alzheimer disease risk in the Ohio and Indiana Amish 95%
- Scalable Bayesian functional GWAS method accounting for multivariate quantitative functional annotations with applications to studying Alzheimer’s disease 93%
Similar papers in this journal
- Multi-Tissue Neocortical Transcriptome-Wide Associations Study Implicates 8 Genes Across 6 Genomic Loci in Alzheimer's Disease 94%
- A multilayered post-GWAS assessment on genetic susceptibility to pancreatic cancer 92%
- Investigation of an LPA KIV-2 nonsense mutation in 11,000 individuals: the importance of linkage disequilibrium structure in LPA genetics. 92%
Similar papers in this journal
- Human-lineage-specific genomic elements: relevance to neurodegenerative disease and APOE transcript usage 95%
- A meta-analysis of epigenome-wide association studies in Alzheimer's disease highlights novel differentially methylated loci across cortex 95%
- A public resource of single cell transcriptomes and multiscale networks from persons with and without Alzheimer's disease 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.