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See detailGenetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing
Kunkle, Brian W.; Grenier-Boley, Benjamin; Sims, Rebecca et al

in Nature Genetics (2019), 51(3), 414

Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of ... [more ▼]

Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer's or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and A$\beta$ processing are associated not only with early-onset autosomal dominant Alzheimer's disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 × 10−7), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education. [less ▲]

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See detailComputational Systems Biology Approach for the Study of Rheumatoid Arthritis: From a Molecular Map to a Dynamical Model
Singh, Vidisha; Ostaszewski, Marek UL; Kalliolias, George D. et al

in Genomics and Computational Biology (2017)

In this work we present a systematic effort to summarize current biological pathway knowledge concerning Rheumatoid Arthritis (RA). We are constructing a detailed molecular map based on exhaustive ... [more ▼]

In this work we present a systematic effort to summarize current biological pathway knowledge concerning Rheumatoid Arthritis (RA). We are constructing a detailed molecular map based on exhaustive literature scanning, strict curation criteria, re-evaluation of previously published attempts and most importantly experts’ advice. The RA map will be web-published in the coming months in the form of an interactive map, using the MINERVA platform, allowing for easy access, navigation and search of all molecular pathways implicated in RA, serving thus, as an on line knowledgebase for the disease. Moreover the map could be used as a template for Omics data visualization offering a first insight about the pathways affected in different experimental datasets. The second goal of the project is a dynamical study focused on synovial fibroblasts’ behavior under different initial conditions specific to RA, as recent studies have shown that synovial fibroblasts play a crucial role in driving the persistent, destructive characteristics of the disease. Leaning on the RA knowledgebase and using the web platform Cell Collective, we are currently building a Boolean large scale dynamical model for the study of RA fibroblasts’ activation [less ▲]

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See detailRare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease
Sims, Rebecca; van der Lee, Sven J.; Naj, Adam C. et al

in Nature Genetics (2017), 49

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