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Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer's disease risk.
- Source :
-
Nature genetics [Nat Genet] 2019 Mar; Vol. 51 (3), pp. 404-413. Date of Electronic Publication: 2019 Jan 07. - Publication Year :
- 2019
-
Abstract
- Alzheimer's disease (AD) is highly heritable and recent studies have identified over 20 disease-associated genomic loci. Yet these only explain a small proportion of the genetic variance, indicating that undiscovered loci remain. Here, we performed a large genome-wide association study of clinically diagnosed AD and AD-by-proxy (71,880 cases, 383,378 controls). AD-by-proxy, based on parental diagnoses, showed strong genetic correlation with AD (r <subscript>g</subscript> = 0.81). Meta-analysis identified 29 risk loci, implicating 215 potential causative genes. Associated genes are strongly expressed in immune-related tissues and cell types (spleen, liver, and microglia). Gene-set analyses indicate biological mechanisms involved in lipid-related processes and degradation of amyloid precursor proteins. We show strong genetic correlations with multiple health-related outcomes, and Mendelian randomization results suggest a protective effect of cognitive ability on AD risk. These results are a step forward in identifying the genetic factors that contribute to AD risk and add novel insights into the neurobiology of AD.
Details
- Language :
- English
- ISSN :
- 1546-1718
- Volume :
- 51
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Nature genetics
- Publication Type :
- Academic Journal
- Accession number :
- 30617256
- Full Text :
- https://doi.org/10.1038/s41588-018-0311-9