| Title: | Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer's disease risk |
| Journal: | Nat Genet |
| Published: | 1 Mar 2019 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/30617256/ |
| DOI: | https://doi.org/10.1038/s41588-018-0311-9 |
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. These loci only explain a small proportion of the genetic risk for developing AD, indicating that undiscovered loci remain. Although there are very few individuals with Alzheimer s in UK Biobank, this study leveraged participant reports of their parents AD diagnoses to create a proxy measure of inherited genetic risk. Combining this sample with other studies of clinically diagnosed AD (71,880 cases and 383,378 controls in total) resulted in greater statistical power to identify associated genomic loci. Altogether we identified 29 disease-associated loci (9 novel and 20 validating previous findings), implicating 215 potential causative genes. The associated genes are most active in immune-related tissues and cell types (i.e. spleen, liver, and microglia). Gene-set analyses indicated that the associated genes are involved in biological mechanisms such as lipid-related processes and degradation of amyloid precursor proteins. This link was already known in relation to the APOE gene, the most robust genetic risk factor for AD, but these findings strengthen the hypothesis that AD is caused by an interplay between inflammation and lipids in the brain. This study also showed genetic correlations between AD and multiple health-related outcomes, including a protective effect of cognitive ability against the risk of developing AD. These results are a step forward in identifying the genetic factors that contribute to AD and add novel insights into its neurobiology.1 Author
- Jansen IE et al.
1 Application
| Application ID | |
|---|---|
| 16406 | Causes of individual differences in cognitive and mental health |
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