Unknown

Dataset Information

0

Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer's disease risk.


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 (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.

SUBMITTER: Jansen IE 

PROVIDER: S-EPMC6836675 | BioStudies | 2019-01-01

REPOSITORIES: biostudies

Similar Datasets

2017-01-01 | S-EPMC5622124 | BioStudies
2011-01-01 | S-EPMC3044851 | BioStudies
2019-01-01 | S-EPMC6783343 | BioStudies
2016-01-01 | S-EPMC4864940 | BioStudies
2019-01-01 | S-EPMC6365681 | BioStudies
2019-01-01 | S-EPMC7193309 | BioStudies
2020-01-01 | S-EPMC6367065 | BioStudies
2015-01-01 | S-EPMC4486643 | BioStudies
2020-01-01 | S-EPMC7181749 | BioStudies
2020-01-01 | S-EPMC7575686 | BioStudies