34 research outputs found
Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease
We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development
The genetic architecture of the human cerebral cortex
The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder
Ronald Paulson. Don Quixote in England: The Aesthetics of Laughter. Baltimore, Md.: The Johns Hopkins University Press. 1997. Pp. xx, 242. $35.00. ISBN 0-8018-5695-7.
Jane Austen's `Sir Charles Grandison.' Brian Southam An Understanding of Jane Austen's Novels: Character, Value and Ironic Perspective. John Odmark The Thread of Connection: Aspects of Fate in the Novels of Jane Austen and Others. C. C. Barfoot Jane Austen in a Social Context. David Monaghan
The true story of the novel /
Originally published: 1996.Electronic access restricted; authentication may be required:978081352453
Scoping the landscape and the effect of advanced nurse practitioners (ANP) in supporting healthcare provision in Ireland in the 21st Century: An integrative review
To scope the landscape and identify the effect of ANPs on care provision in Ireland, eight academic databases (CINAHL, Embase, PsycINFO, Scopus, Medline and Academic Search Complete, Cochrane, Web of Science) relevant to nursing and health will be searched