The risk of Alzheimer disease is substantially influenced by genetic factors. A new genome-wide association study of more than 600,000 individuals identifies nine novel Alzheimer disease risk genes, raising the total count of independent risk loci to 29.
This is a preview of subscription content, access via your institution
Access options
References
Veitch, D. P. et al. Understanding disease progression and improving Alzheimer’s disease clinical trials: recent highlights from the Alzheimer’s Disease Neuroimaging Initiative. Alzheimers Dement. 15, 106–152 (2019).
Tanzi, R. E. & Bertram, L. Twenty years of the Alzheimer’s disease amyloid hypothesis: a genetic perspective. Cell 120, 545–555 (2005).
Lambert, J. C. et al. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nat. Genet. 45, 1452–1458 (2013).
Jansen, I. E. et al. Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer’s disease risk. Nat. Genet. https://doi.org/10.1038/s41588-018-0311-9 (2019).
Bertram, L. et al. Genome-wide association analysis reveals putative Alzheimer’s disease susceptibility loci in addition to APOE. Am. J. Hum. Genet. 83, 623–632 (2008).
Suh, J. et al. ADAM10 missense mutations potentiate β-amyloid accumulation by impairing prodomain chaperone function. Neuron 80, 385–401 (2013).
Bycroft, C. et al. The UK Biobank resource with deep phenotyping and genomic data. Nature 562, 203–209 (2018).
Liu, J. Z., Erlich, Y. & Pickrell, J. K. Case-control association mapping by proxy using family history of disease. Nat. Genet. 49, 325–331 (2017).
Zuk, O. et al. The mystery of missing heritability: genetic interactions create phantom heritability. Proc. Natl Acad. Sci. USA 109, 1193–1198 (2012).
Escott-Price, V. et al. Polygenic risk score analysis of pathologically confirmed Alzheimer disease. Ann. Neurol. 82, 311–314 (2017).
Acknowledgements
L.B. is supported by grants from the Deutsche Forschungsgemeinschaft (DFG), the European Research Council (ERC) and the Cure Alzheimer’s Fund (CAF). R.E.T. is supported by the Cure Alzheimer’s Fund and the JPB Foundation.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Rights and permissions
About this article
Cite this article
Bertram, L., Tanzi, R.E. Alzheimer disease risk genes: 29 and counting. Nat Rev Neurol 15, 191–192 (2019). https://doi.org/10.1038/s41582-019-0158-4
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41582-019-0158-4