Genome-wide interaction analysis of pathological hallmarks in Alzheimer's disease

Wang, Hui; Yang, Jingyun; Schneider, Julie A.; Jager, Philip L. De; Bennett, David A.; Zhang, Hongyu

doi:10.1016/j.neurobiolaging.2020.04.025

Cited by 72 publications

(75 citation statements)

References 50 publications

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“…We conducted comparative analysis of seven DEGs commonly found in the two sets of RNA‐seq analyses with the results in the previously reported GWAS 25 . Four of seven differentially expressed genes identified in human GWAS studies, were tentatively reported as loci associated with human neurological diseases: Slc8a3 for bipolar disorder, 41 Pmvk for Parkinson's disease, 42 Kcnt2 and Dusp18 for Alzheimer's disease, 43 and Kcnt2 for insomnia and chronotype traits 44,45 . These diseases are not directly related to tameness or domestication in animals; however, combined studies on human GWAS and DEGs between tamed and non‐tamed mice indicate that these genes are playing important roles in maintaining a variety of normal functions in the brains.…”

Section: Discussionmentioning

confidence: 99%

“…We conducted comparative analysis of seven DEGs commonly found in the two sets of RNA-seq analyses with the results in the previously reported GWAS. 25 Four of seven differentially expressed genes identified in human GWAS studies, were tentatively reported as loci associated with human neurological diseases: Slc8a3 for bipolar disorder, 41 Pmvk for Parkinson's disease, 42 Kcnt2 and Dusp18 for Alzheimer's disease, 43 and…”

Section: Discussionmentioning

confidence: 99%

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Combined change of behavioral traits for domestication and gene‐networks in mice selectively bred for active tameness

Matsumoto

Nagayama

Nakaoka

et al. 2021

Genes Brain and Behavior

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Tameness is a major element of animal domestication and involves two components: motivation to approach humans (active tameness) and reluctance to avoid humans (passive tameness). To understand the behavioral and genetic mechanisms of active tameness in mice, we had previously conducted selective breeding for long durations of contact and heading toward human hands in an active tameness test using a wild‐derived heterogeneous stock. Although the study showed a significant increase in contacting and heading with the 12th generation of breeding, the effect on other behavioral indices related to tameness and change of gene expression levels underlying selective breeding was unclear. Here, we analyzed nine tameness‐related traits at a later stage of selective breeding and analyzed how gene expression levels were changed by the selective breeding. We found that five traits, including contacting and heading, showed behavioral change in the selective groups comparing to the control through the generations. Furthermore, we conducted cluster analyses to evaluate the relationships among the nine traits and found that contacting and heading combined in an independent cluster in the selected groups, but not in the control groups. RNA‐Seq of hippocampal tissue revealed differential expression of 136 genes between the selection and control groups, while the pathway analysis identified the networks associated with these genes. These results suggest that active tameness was hidden in the control groups but became apparent in the selected populations by selective breeding, potentially driven by changes in gene expression networks.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Combined change of behavioral traits for domestication and gene‐networks in mice selectively bred for active tameness

Matsumoto

Nagayama

Nakaoka

et al. 2021

Genes Brain and Behavior

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“…A shift from aerobic glycolysis to OxPhos is required for neural stem cell differentiation and neural survival (Zheng et al, 2016); many neurodegenerative diseases are associated with defects in OxPhos (Koopman et al, 2013). Interestingly, four different single nucleotide polymorphisms (SNP) in FAM214A introns have been linked to more severe Alzheimer’s disease or neurofibrillary tangles in genome wide association studies while another SNP in a transcription factor-binding region was associated with increased general intelligence (p-value for all variants≤5×10 −6 ; https://www.ebi.ac.uk/gwas/search?query=FAM214A), Sherva et al, 2020; Beecham et al, 2014; Wang et al, 2020; Davies et al, 2018). The importance of OxPhos enhancers for brain function is demonstrated by the many neurodegenerative diseases connected to defects in PGC-1 (Zheng et al, 2010; Cui et al, 2006; Weydt et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

A genetic program boosts mitochondrial function to power macrophage tissue invasion

Emtenani

Martin

Gyoergy

et al. 2021

Preprint

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Metabolic adaptation to changing demands underlies homeostasis. During inflammation or metastasis, cells leading migration into challenging environments require an energy boost, however what controls this capacity is unknown. We identify a previously unstudied nuclear protein, Atossa, as changing metabolism in Drosophila melanogaster immune cells to promote tissue invasion. Atossa's vertebrate orthologs, FAM214A-B can fully substitute for Atossa, indicating functional conservation from flies to mammals. Atossa increases mRNA levels of Porthos, an unstudied RNA helicase and two metabolic enzymes, LKR/SDH and GR/HPR. Porthos increases translation of a gene subset, including those affecting mitochondrial functions, the electron transport chain, and metabolism. Respiration measurements and metabolomics indicate that Atossa and Porthos power up mitochondrial oxidative phosphorylation to produce sufficient energy for pioneer macrophages to forge a path into tissues. As increasing oxidative phosphorylation enables many crucial physiological responses, this unique genetic program may modulate a wide range of cellular behaviors beyond migration.

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“…This is noteworthy, since the blood vessel is of relevance in the PH and neuronal apoptosis in the prognosis. Interestingly, several of the genes from the genes included in these loci have been associated in other GWAS studies to aggregated amyloid-β peptide and tau protein such as PCSK5 or EIF3H [30]. SEMA3A has been associated with cortical thickness and white matter microstructure measurement [31], parameters related to cognitive impairment.…”

Section: Discussionmentioning

confidence: 99%

RP11-362K2.2:RP11-767I20.1 Genetic Variation Is Associated with Post-Reperfusion Therapy Parenchymal Hematoma. A GWAS Meta-Analysis

Muiño¹,

Cárcel‐Márquez²,

Carrera³

et al. 2021

JCM

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Stroke is one of the most common causes of death and disability. Reperfusion therapies are the only treatment available during the acute phase of stroke. Due to recent clinical trials, these therapies may increase their frequency of use by extending the time-window administration, which may lead to an increase in complications such as hemorrhagic transformation, with parenchymal hematoma (PH) being the more severe subtype, associated with higher mortality and disability rates. Our aim was to find genetic risk factors associated with PH, as that could provide molecular targets/pathways for their prevention/treatment and study its genetic correlations to find traits sharing genetic background. We performed a GWAS and meta-analysis, following standard quality controls and association analysis (fastGWAS), adjusting age, NIHSS, and principal components. FUMA was used to annotate, prioritize, visualize, and interpret the meta-analysis results. The total number of patients in the meta-analysis was 2034 (216 cases and 1818 controls). We found rs79770152 having a genome-wide significant association (beta 0.09, p-value 3.90 × 10−8) located in the RP11-362K2.2:RP11-767I20.1 gene and a suggestive variant (rs13297983: beta 0.07, p-value 6.10 × 10−8) located in PCSK5 associated with PH occurrence. The genetic correlation showed a shared genetic background of PH with Alzheimer’s disease and white matter hyperintensities. In addition, genes containing the ten most significant associations have been related to aggregated amyloid-β, tau protein, white matter microstructure, inflammation, and matrix metalloproteinases.

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Genome-wide interaction analysis of pathological hallmarks in Alzheimer's disease

Cited by 72 publications

References 50 publications

Combined change of behavioral traits for domestication and gene‐networks in mice selectively bred for active tameness

Combined change of behavioral traits for domestication and gene‐networks in mice selectively bred for active tameness

A genetic program boosts mitochondrial function to power macrophage tissue invasion

RP11-362K2.2:RP11-767I20.1 Genetic Variation Is Associated with Post-Reperfusion Therapy Parenchymal Hematoma. A GWAS Meta-Analysis

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