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Integrated Systems Approach Identifies Genetic Nodes and Networks in Late-Onset Alzheimer’s Disease
TLDR
The causal network structure is a useful predictor of response to gene perturbations and presents a framework to test models of disease mechanisms underlying LOAD. Expand
An xQTL map integrates the genetic architecture of the human brain’s transcriptome and epigenome
  • B. Ng, Charles C White, +9 authors P. D. De Jager
  • Biology, Medicine
  • Nature Neuroscience
  • 4 September 2017
We report a multi-omic resource generated by applying quantitative trait locus (xQTL) analyses to RNA sequence, DNA methylation and histone acetylation data from the dorsolateral prefrontal cortex ofExpand
A molecular network of the aging human brain provides insights into the pathology and cognitive decline of Alzheimer’s disease
TLDR
The construction and validation of a molecular network of the aging human frontal cortex is reported, constructed and validated from RNA sequence data from 478 individuals and identified genes that affect cognitive decline or neuropathology in Alzheimer's disease. Expand
A molecular signature of depression in the amygdala.
TLDR
These studies demonstrate that the biological liability to major depression is reflected in a persistent molecular pathology that affects the amygdala, and support the hypothesis of maladaptive changes in this brain region as a putative primary pathology in major depression. Expand
Beyond modules and hubs: the potential of gene coexpression networks for investigating molecular mechanisms of complex brain disorders
TLDR
To accelerate coexpression research beyond modules and hubs, some emerging directions for coexpression network research that are especially relevant to complex brain disease are highlighted, including the centrality–lethality relationship, integration with machine learning approaches and network pharmacology. Expand
Variants in triggering receptor expressed on myeloid cells 2 are associated with both behavioral variant frontotemporal lobar degeneration and Alzheimer's disease
TLDR
Analysis of a consanguineous family segregating autosomal recessive behavioral variant FTLD from Antioquia, Colombia suggests that a mutational burden in TREM2 may serve as a risk factor for neurodegenerative disease in general, and that potentially this class of T REM2 variant carriers with dementia should be considered as having a molecularly distinct form of neurodegenersative disease. Expand
Genetic variants in Alzheimer disease — molecular and brain network approaches
TLDR
How the study of molecular, cellular and brain networks provides additional information on the effects of LOAD-associated genetic variants at multiple biophysical scales is discussed and the clinical potential of mechanistically coupling genetic variants and disease phenotypes with multiscale brain models is highlighted. Expand
A multi-omic atlas of the human frontal cortex for aging and Alzheimer’s disease research
We initiated the systematic profiling of the dorsolateral prefrontal cortex obtained from a subset of autopsied individuals enrolled in the Religious Orders Study (ROS) or the Rush Memory and AgingExpand
Brain xQTL map: integrating the genetic architecture of the human brain transcriptome and epigenome
TLDR
The utility of the new resource, xQTL Serve, is illustrated in prioritizing the cell type most affected by an xQ TL and in enhancing genome wide association studies (GWAS) as it is reported 18 additional CNS disease susceptibility loci after re-analyzing published studies. Expand
Seasonal plasticity of cognition and related biological measures in adults with and without Alzheimer disease: Analysis of multiple cohorts
TLDR
The persistence of robust seasonal plasticity in cognition and its neurobiological correlates, even in the context of concomitant AD pathology, suggests that targeting environmental or behavioral drivers of seasonal cognitive plasticity, or the key transcription factors and genes identified in this study as potentially mediating these effects, may allow us to substantially improve cognition in adults with and without AD. Expand
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