scholarly journals Association of MAPT haplotypes with Alzheimer’s disease risk and MAPT brain gene expression levels

2014 ◽  
Vol 6 (4) ◽  
pp. 39 ◽  
Author(s):  
Mariet Allen ◽  
Michaela Kachadoorian ◽  
Zachary Quicksall ◽  
Fanggeng Zou ◽  
High Chai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Risk ◽  
Expression Levels ◽  
Brain Gene Expression ◽  
Gene Expression Levels

scholarly journals Enhancer variants associated with Alzheimer’s disease affect gene expression via chromatin looping

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Masataka Kikuchi ◽  
Norikazu Hara ◽  
Mai Hasegawa ◽  
Akinori Miyashita ◽  
Ryozo Kuwano ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Regulatory Elements ◽  
Genome Wide Association Studies ◽  
Expression Levels ◽  
Chromatin Loops ◽  
Coding Regions ◽  
Affect Gene Expression ◽  
Gene Expression Levels

Abstract Background Genome-wide association studies (GWASs) have identified single-nucleotide polymorphisms (SNPs) that may be genetic factors underlying Alzheimer’s disease (AD). However, how these AD-associated SNPs (AD SNPs) contribute to the pathogenesis of this disease is poorly understood because most of them are located in non-coding regions, such as introns and intergenic regions. Previous studies reported that some disease-associated SNPs affect regulatory elements including enhancers. We hypothesized that non-coding AD SNPs are located in enhancers and affect gene expression levels via chromatin loops. Methods To characterize AD SNPs within non-coding regions, we extracted 406 AD SNPs with GWAS p-values of less than 1.00 × 10− 6 from the GWAS catalog database. Of these, we selected 392 SNPs within non-coding regions. Next, we checked whether those non-coding AD SNPs were located in enhancers that typically regulate gene expression levels using publicly available data for enhancers that were predicted in 127 human tissues or cell types. We sought expression quantitative trait locus (eQTL) genes affected by non-coding AD SNPs within enhancers because enhancers are regulatory elements that influence the gene expression levels. To elucidate how the non-coding AD SNPs within enhancers affect the gene expression levels, we identified chromatin-chromatin interactions by Hi-C experiments. Results We report the following findings: (1) nearly 30% of non-coding AD SNPs are located in enhancers; (2) eQTL genes affected by non-coding AD SNPs within enhancers are associated with amyloid beta clearance, synaptic transmission, and immune responses; (3) 95% of the AD SNPs located in enhancers co-localize with their eQTL genes in topologically associating domains suggesting that regulation may occur through chromatin higher-order structures; (4) rs1476679 spatially contacts the promoters of eQTL genes via CTCF-CTCF interactions; (5) the effect of other AD SNPs such as rs7364180 is likely to be, at least in part, indirect through regulation of transcription factors that in turn regulate AD associated genes. Conclusion Our results suggest that non-coding AD SNPs may affect the function of enhancers thereby influencing the expression levels of surrounding or distant genes via chromatin loops. This result may explain how some non-coding AD SNPs contribute to AD pathogenesis.

scholarly journals A candidate regulatory variant at the TREM gene cluster associates with decreased Alzheimer's disease risk and increased TREML1 and TREM2 brain gene expression

2017 ◽  
Vol 13 (6) ◽  
pp. 663-673 ◽  
Author(s):  
Minerva M. Carrasquillo ◽  
Mariet Allen ◽  
Jeremy D. Burgess ◽  
Xue Wang ◽  
Samantha L. Strickland ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gene Cluster ◽  
Disease Risk ◽  
Brain Gene Expression ◽  
Regulatory Variant

O3-11-03: Genetic association of variants with late-onset Alzheimer's disease risk and brain gene expression

2012 ◽  
Vol 8 (4S_Part_12) ◽  
pp. P451-P451 ◽  
Author(s):  
Mariet Allen ◽  
Fanggeng Zou ◽  
High Seng Chai ◽  
Curtis Younkin ◽  
Julia Crook ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genetic Association ◽  
Disease Risk ◽  
Late Onset ◽  
Brain Gene Expression

O2-10-04: A Regulatory Variant at the TREM Gene Cluster Associates with Decreased Alzheimer’s Disease Risk and Increased TREML1 and TREM2 Brain Gene Expression

2016 ◽  
Vol 12 ◽  
pp. P251-P252 ◽  
Author(s):  
Minerva M. Carrasquillo ◽  
Mariet Allen ◽  
Jeremy D. Burgess ◽  
Samantha L. Strickland ◽  
Shivani Aryal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gene Cluster ◽  
Disease Risk ◽  
Brain Gene Expression ◽  
Regulatory Variant

scholarly journals Consistent Genes Associated With Structural Changes in Clinical Alzheimer’s Disease Spectrum

2021 ◽  
Author(s):  
Jinping Xu ◽  
Chao Wang ◽  
Jinhuan Zhang ◽  
Junjie Zhuo ◽  
Qingmao Hu
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Structural Changes ◽  
Cognitive Impairments ◽  
Functional Enrichment ◽  
Positive Regulation ◽  
Negatively Associated ◽  
Expression Levels ◽  
Gene Expression Levels

Abstract Background:Previous studies showed no obvious symptoms but subtle structural brain changes in a long preclinical stage of Alzheimer's disease (AD), then localized cortical and sub-cortical atrophy in MCI, and spread aggressively to nearly whole brain neurodegeneration in AD. However, the neurobiological and pathogenic substrates underlying these structural changes across AD spectrum remain largely understood.Methods: We obtained structural MRI imaging from ADNI datasets, including 83 early-stage mild cognitive impairments (EMCI), 83 late-stage mild cognitive impairments (LMCI), 83 AD, and 83 normal controls (NC), and aimed to explore structural changes across the full clinical AD spectrum and their genetic mechanism. Partial least square regressions and Spearman correlations were performed to explore how these changes associated with gene expression level obtained from Allen Human Brain Atlas. Finally, functional enrichment analyses were conducted using Metascape analysis to explore ontological pathways of the consistent genes. Results:We identified significant volume atrophy in left thalamus, left cerebellum, and bilateral middle frontal gyrus across AD spectrum. These structural changes were positively associated with gene expression levels of ABCA7, SORCS1, SORL1, PILRA, PFDN1, PLXNA4, TRIP4, and CD2AP, whereas were negatively associated with gene expression levels of CD33, PLCG2, APOE, and ECHDC3 for all three groups. Moreover, these results were verified in sub-groups of converted and stable EMCI and LMCI. Further gene enrichment analyses revealed that these positively associated genes were mainly involved in positive regulation of cellular protein localization and negative regulation of cellular component organization, whereas the negatively associated genes were mainly involved in positive regulation of iron transport. Conclusions:Overall, these results suggested that structural changes in prodromal and clinical AD might result from interaction of the same gene lists, which offered a better understanding of biological mechanisms underlying structural changes in prodromal and clinical AD.

P1-229: Genome-Wide Association Study of Brain Gene Expression Levels (eGWAS)

2011 ◽  
Vol 7 ◽  
pp. S184-S184
Author(s):  
Nilufer Ertekin-Taner ◽  
Fanggeng Zou ◽  
High Chai ◽  
Curtis Younkin ◽  
Julia Crook ◽  
...  
Keyword(s):  
Gene Expression ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Expression Levels ◽  
Brain Gene Expression ◽  
Genome Wide ◽  
Gene Expression Levels

scholarly journals Brain gene expression patterns differentiate mild cognitive impairment from normal aged and Alzheimer's disease

2014 ◽  
Vol 35 (9) ◽  
pp. 1961-1972 ◽  
Author(s):  
Nicole C. Berchtold ◽  
Marwan N. Sabbagh ◽  
Thomas G. Beach ◽  
Ronald C. Kim ◽  
David H. Cribbs ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Brain Gene Expression

Rs4878104 contributes to Alzheimer’s disease risk and regulates DAPK1 gene expression

2017 ◽  
Vol 38 (7) ◽  
pp. 1255-1262 ◽  
Author(s):  
Yang Hu ◽  
Liang Cheng ◽  
Ying Zhang ◽  
Weiyang Bai ◽  
Wenyang Zhou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Risk

scholarly journals A Comparison of Brain Gene Expression Levels in Domesticated and Wild Animals

PLoS Genetics ◽  
2012 ◽  
Vol 8 (9) ◽  
pp. e1002962 ◽  
Author(s):  
Frank W. Albert ◽  
Mehmet Somel ◽  
Miguel Carneiro ◽  
Ayinuer Aximu-Petri ◽  
Michel Halbwax ◽  
...  
Keyword(s):  
Gene Expression ◽  
Wild Animals ◽  
Expression Levels ◽  
Brain Gene Expression ◽  
Gene Expression Levels
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