Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer's disease risk.
Jansen IE, Savage JE, Watanabe K et al.
Publication Details
Comprehensive information about this research publication
Abstract
Summary of the research findings
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 (rg = 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.
24,087 European ancestry cases, 55,058 European ancestry controls
Study Statistics
Key metrics and study information
AI-Generated Summary
AI-generated by DNAGENICSIndependent AI summary of health and genetic findings from the published study
Important: This summary is AI-generated by DNAGENICS for informational purposes only. It was not created by, affiliated with, or endorsed by the researchers behind the original publication, and is based solely on that published research. It may contain errors or omissions. DNAGENICS disclaims all liability for any inaccuracies or consequences arising from use of this information. Verify all information against the original publication. This is not professional scientific review or medical advice.
AI Summary In Progress
Our AI-generated summary of this publication is being prepared. Please check back soon.