A Computational Network Biology Approach to Uncover Novel Genes Related to Alzheimer’s Disease

2016 ◽  
pp. 435-446 ◽  
Author(s):  
Andreas Zanzoni
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Network Biology ◽  
Novel Genes

scholarly journals Integrated DNA methylation and gene expression profiling across multiple brain regions implicate novel genes in Alzheimer’s disease

2019 ◽  
Vol 137 (4) ◽  
pp. 557-569 ◽  
Author(s):  
Stephen A. Semick ◽  
Rahul A. Bharadwaj ◽  
Leonardo Collado-Torres ◽  
Ran Tao ◽  
Joo Heon Shin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dna Methylation ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Brain Regions ◽  
Novel Genes

Identification of Novel Genes Associated with Cortical Thickness in Alzheimer’s Disease: Systems Biology Approach to Neuroimaging Endophenotype

2020 ◽  
Vol 75 (2) ◽  
pp. 531-545 ◽  
Author(s):  
Bo-Hyun Kim ◽  
Yong-Ho Choi ◽  
Jin-Ju Yang ◽  
SangYun Kim ◽  
Kwangsik Nho ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Systems Biology ◽  
Cortical Thickness ◽  
Novel Genes

scholarly journals Genome-wide analysis reveals novel genes influencing temporal lobe structure with relevance to neurodegeneration in Alzheimer's disease

NeuroImage ◽  
2010 ◽  
Vol 51 (2) ◽  
pp. 542-554 ◽  
Author(s):  
Jason L. Stein ◽  
Xue Hua ◽  
Jonathan H. Morra ◽  
Suh Lee ◽  
Derrek P. Hibar ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Temporal Lobe ◽  
Novel Genes ◽  
Genome Wide Analysis ◽  
Genome Wide

scholarly journals Integrated DNA methylation and gene expression profiling across multiple brain regions implicate novel genes in Alzheimer’s disease

2018 ◽  
Author(s):  
Stephen A. Semick ◽  
Rahul A. Bharadwaj ◽  
Leonardo Collado-Torres ◽  
Ran Tao ◽  
Joo Heon Shin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dna Methylation ◽  
Neurodegenerative Disorder ◽  
Late Onset ◽  
Brain Regions ◽  
Epigenetic Mechanism ◽  
Novel Genes ◽  
Age Related

AbstractBackgroundLate-onset Alzheimer’s disease (AD) is a complex age-related neurodegenerative disorder that likely involves epigenetic factors. To better understand the epigenetic state associated with AD represented as variation in DNA methylation (DNAm), we surveyed 420,852 DNAm sites from neurotypical controls (N=49) and late-onset AD patients (N=24) across four brain regions (hippocampus, entorhinal cortex, dorsolateral prefrontal cortex and cerebellum).ResultsWe identified 858 sites with robust differential methylation, collectively annotated to 772 possible genes (FDR<5%, within 10kb). These sites were overrepresented in AD genetic risk loci (p=0.00655), and nearby genes were enriched for processes related to cell-adhesion, immunity, and calcium homeostasis (FDR<5%). We analyzed corresponding RNA-seq data to prioritize 130 genes within 10kb of the differentially methylated sites, which were differentially expressed and had expression levels associated with nearby DNAm levels (p<0.05). This validated gene set includes previously reported (e.g. ANK1, DUSP22) and novel genes involved in Alzheimer’s disease, such as ANKRD30B.ConclusionsThese results highlight DNAm changes in Alzheimer’s disease that have gene expression correlates, implicating DNAm as an epigenetic mechanism underlying pathological molecular changes associated with AD. Furthermore, our framework illustrates the value of integrating epigenetic and transcriptomic data for understanding complex disease.

scholarly journals Hippocampal transcriptome-wide association study and neurobiological pathway analysis for Alzheimer’s disease

PLoS Genetics ◽  
2021 ◽  
Vol 17 (2) ◽  
pp. e1009363
Author(s):  
Nana Liu ◽  
Jiayuan Xu ◽  
Huaigui Liu ◽  
Shijie Zhang ◽  
Miaoxin Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Association Study ◽  
Meta Analysis ◽  
Hippocampal Volume ◽  
Genome Wide Association ◽  
Novel Genes ◽  
Genome Wide ◽  
Mapping Models

Genome-wide association studies (GWASs) have identified multiple susceptibility loci for Alzheimer’s disease (AD), which is characterized by early and progressive damage to the hippocampus. However, the association of hippocampal gene expression with AD and the underlying neurobiological pathways remain largely unknown. Based on the genomic and transcriptomic data of 111 hippocampal samples and the summary data of two large-scale meta-analyses of GWASs, a transcriptome-wide association study (TWAS) was performed to identify genes with significant associations between hippocampal expression and AD. We identified 54 significantly associated genes using an AD-GWAS meta-analysis of 455,258 individuals; 36 of the genes were confirmed in another AD-GWAS meta-analysis of 63,926 individuals. Fine-mapping models further prioritized 24 AD-related genes whose effects on AD were mediated by hippocampal expression, including APOE and two novel genes (PTPN9 and PCDHA4). These genes are functionally related to amyloid-beta formation, phosphorylation/dephosphorylation, neuronal apoptosis, neurogenesis and telomerase-related processes. By integrating the predicted hippocampal expression and neuroimaging data, we found that the hippocampal expression of QPCTL and ERCC2 showed significant difference between AD patients and cognitively normal elderly individuals as well as correlated with hippocampal volume. Mediation analysis further demonstrated that hippocampal volume mediated the effect of hippocampal gene expression (QPCTL and ERCC2) on AD. This study identifies two novel genes associated with AD by integrating hippocampal gene expression and genome-wide association data and reveals candidate hippocampus-mediated neurobiological pathways from gene expression to AD.

scholarly journals Integrative analysis of eQTL and GWAS summary statistics reveals novel genes related to Alzheimer's disease

2021 ◽  
Vol 17 (S5) ◽  
Author(s):  
Pradeep Varathan ◽  
Priyanka Gorijala ◽  
Tanner Y. Jacobson ◽  
Kwangsik Nho ◽  
Shannon L. Risacher ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Integrative Analysis ◽  
Summary Statistics ◽  
Novel Genes

scholarly journals Genome‐wide association study of rate of cognitive decline in Alzheimer's disease patients identifies novel genes and pathways

2020 ◽  
Vol 16 (8) ◽  
pp. 1134-1145
Author(s):  
Richard Sherva ◽  
Alden Gross ◽  
Shubhabrata Mukherjee ◽  
Ryan Koesterer ◽  
Philippe Amouyel ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Novel Genes ◽  
Genome Wide

scholarly journals Gene-based analysis in HRC imputed genome wide association data identifies three novel genes for Alzheimer’s disease

PLoS ONE ◽  
2019 ◽  
Vol 14 (7) ◽  
pp. e0218111 ◽  
Author(s):  
Emily Baker ◽  
Rebecca Sims ◽  
Ganna Leonenko ◽  
Aura Frizzati ◽  
Janet C. Harwood ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genome Wide Association ◽  
Novel Genes ◽  
Genome Wide ◽  
Association Data
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