Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer’s disease risk
By I. Jansen, J. Savage, Kyoko Watanabe, J. Bryois, Dylan M. Williams, S. Steinberg, J. Sealock, I. Karlsson, Sara Hägg, L. Athanasiu and 43 more. Nature Genetics, 2019
2,006 citations recorded by the source corpus.
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. Genome-wide meta-analysis of clinically diagnosed Alzheimer’s disease (AD) and AD-by-proxy (71,880 AD cases, 383,378 controls) identifies new loci and functional pathways that contribute to AD risk.
Subfields: Genetics, Molecular Biology, Physiology
View Paper: https://www.semanticscholar.org/paper/0585533f99b3aa700aa674590012c96739b8eff2
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Molecular Biology
In Physiology
Citations in the corpus
- The neuropathological diagnosis of Alzheimer’s disease (2019, background): “Other risk factors for LOAD including TREM2, ADAM10 and PLD3 have been identified using genome wide association studies to implicate nearly 30 genes that not only affect APP and tau directly but also modulate cholesterol metabolism, endocytosis and immune response, among those with known functions [”
- The genetic architecture of the human cerebral cortex (2020, neutral): “28 aggression(70), Alzheimer's disease(71), loneliness(72), cigarettes smoked per day(73),”