| Title: | Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer's disease risk |
| Journal: | Nature Genetics |
| Published: | 7 Jan 2019 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/30617256/ |
| DOI: | https://doi.org/10.1038/s41588-018-0311-9 |
| URL: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6836675 |
| Citations: | 1777 (540 in last 2 years) as of 8 Aug 2024 |
Publication 2711
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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.</p>
13 Keywords
- Adult
- Alzheimer Disease
- Case-Control Studies
- Female
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Male
- Middle Aged
- Polymorphism, Single Nucleotide
- Quantitative Trait Loci
- Risk
- Young Adult
53 Authors
- Iris E. Jansen
- Jeanne E. Savage
- Kyoko Watanabe
- Julien Bryois
- Dylan M. Williams
- Stacy Steinberg
- Julia Sealock
- Ida K. Karlsson
- Sara Hägg
- Lavinia Athanasiu
- Nicola Voyle
- Petroula Proitsi
- Aree Witoelar
- Sven Stringer
- Dag Aarsland
- Ina S. Almdahl
- Fred Andersen
- Sverre Bergh
- Francesco Bettella
- Sigurbjorn Bjornsson
- Anne Brækhus
- Geir Bråthen
- Christiaan de Leeuw
- Rahul S. Desikan
- Srdjan Djurovic
- Logan Dumitrescu
- Tormod Fladby
- Timothy J. Hohman
- Palmi V. Jonsson
- Steven J. Kiddle
- Arvid Rongve
- Ingvild Saltvedt
- Sigrid B. Sando
- Geir Selbæk
- Maryam Shoai
- Nathan G. Skene
- Jon Snaedal
- Eystein Stordal
- Ingun D. Ulstein
- Yunpeng Wang
- Linda R. White
- John Hardy
- Jens Hjerling-Leffler
- Patrick F. Sullivan
- Wiesje M. van der Flier
- Richard Dobson
- Lea K. Davis
- Hreinn Stefansson
- Kari Stefansson
- Nancy L. Pedersen
- Stephan Ripke
- Ole A. Andreassen
- Danielle Posthuma
1 Application
| Application ID | Title |
|---|---|
| 16406 | Causes of individual differences in cognitive and mental health |
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