Possenti Andrea
UniCa About Professors and Researchers Andrea Possenti Research Research outcomes (IRIS)

Andrea Possenti

Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing

Del Zompo, Maria;Squassina, Alessio;
2019-01-01

Abstract

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 Aβ 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.
2019
2019
Inglese
NATURE GENETICS
51
3
414
430
17
WOS:000459947200011
2-s2.0-85063748662
30820047
https://www.nature.com/articles/s41588-019-0358-2
Esperti anonimi
internazionale
scientifica
sì
Kunkle, Brian W; Grenier-Boley, Benjamin; Sims, Rebecca; Bis, Joshua C; Damotte, Vincent; Naj, Adam C; Boland, Anne; Vronskaya, Maria; van der Lee, Sv ...espandi
1.1 Articolo in rivista
info:eu-repo/semantics/article
1 Contributo su Rivista::1.1 Articolo in rivista
262
468
reserved
Files in This Item:
File Size Format  
Nature Genetics.pdf

Solo gestori archivio

Type: versione editoriale
Size 1.76 MB
Format Adobe PDF
& nbsp; View / Open   Request a copy
1.76 MB Adobe PDF & nbsp; View / Open   Request a copy

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Questionnaire and social

Share on:
Impostazioni cookie