Polygenic Risk Score of Longevity Predicts Longer Survival across an Age Continuum

Studying the genome of centenarians may give insights into the molecular mechanisms underlying extreme human longevity and the escape of age-related diseases. Here, we set out to construct polygenic risk scores (PRSs) for longevity and to investigate the functions of longevity-associated variants. Using a cohort of centenarians with...

Genome-wide association study of frontotemporal dementia identifies a C9ORF72 haplotype with a median of 12-G4C2 repeats that predisposes to pathological repeat expansions

Genetic factors play a major role in frontotemporal dementia (FTD). The majority of FTD cannot be genetically explained yet and it is likely that there are still FTD risk loci to be discovered. Common variants have been identified with genome-wide association studies (GWAS), but these studies have not systematically searched for rare variants...

Genetics Contributes to Concomitant Pathology and Clinical Presentation in Dementia with Lewy Bodies

Background: Dementia with Lewy bodies (DLB) is a complex, progressive neurodegenerative disease with considerable phenotypic, pathological, and genetic heterogeneity. Objective: We tested if genetic variants in part explain the heterogeneity in DLB. Methods: We tested the effects of variants previously associated with DLB (near APOE, GBA, and...

Immune response and endocytosis pathways are associated with the resilience against Alzheimer’s disease

Developing Alzheimer’s disease (AD) is influenced by multiple genetic variants that are involved in five major AD-pathways. Per individual, these pathways may differentially contribute to the modification of the AD-risk. The pathways involved in the resilience against AD have thus far been poorly addressed. Here, we investigated to what...

Brain transcriptome atlases: A computational perspective

The immense complexity of the mammalian brain is largely reflected in the underlying molecular signatures of its billions of cells. Brain transcriptome atlases provide valuable insights into gene expression patterns across different brain areas throughout the course of development. Such atlases allow researchers to probe the molecular mechanisms...

Cortical Spreading Depression Causes Unique Dysregulation of Inflammatory Pathways in a Transgenic Mouse Model of Migraine

Familial hemiplegic migraine type 1 (FHM1) is a rare monogenic subtype of migraine with aura caused by mutations in CACNA1A that encodes the α1A subunit of voltage-gated CaV2.1 calcium channels. Transgenic knock-in mice that carry the human FHM1 R192Q missense mutation (‘FHM1 R192Q mice’) exhibit an increased susceptibility to cortical spreading...

BrainScope: Interactive visual exploration of the spatial and temporal human brain transcriptome

Spatial and temporal brain transcriptomics has recently emerged as an invaluable data source for molecular neuroscience. The complexity of such data poses considerable challenges for analysis and visualization. We present BrainScope: A web portal for fast, interactive visual exploration of the Allen Atlases of the adult and developing human...

Pan-cancer subtyping in a 2D-map shows substructures that are driven by specific combinations of molecular characteristics

The use of genome-wide data in cancer research, for the identification of groups of patients with similar molecular characteristics, has become a standard approach for applications in therapy-response, prognosis-prediction, and drug-development. To progress in these applications, the trend is to move from single genome-wide measurements in a...

Visualizing the spatial gene expression organization in the brain through non-linear similarity embeddings

The Allen Brain Atlases enable the study of spatially resolved, genome-wide gene expression patterns across the mammalian brain. Several explorative studies have applied linear dimensionality reduction methods such as Principal Component Analysis (PCA) and classical Multi-Dimensional Scaling (cMDS) to gain insight into the spatial organization...