News & Views | Published:

ALZHEIMER DISEASE

Alzheimer disease risk genes: 29 and counting

Nature Reviews Neurology (2019) | Download Citation

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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    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).

  2. 2.

    Tanzi, R. E. & Bertram, L. Twenty years of the Alzheimer’s disease amyloid hypothesis: a genetic perspective. Cell 120, 545–555 (2005).

  3. 3.

    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).

  4. 4.

    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).

  5. 5.

    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).

  6. 6.

    Suh, J. et al. ADAM10 missense mutations potentiate β-amyloid accumulation by impairing prodomain chaperone function. Neuron 80, 385–401 (2013).

  7. 7.

    Bycroft, C. et al. The UK Biobank resource with deep phenotyping and genomic data. Nature 562, 203–209 (2018).

  8. 8.

    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).

  9. 9.

    Zuk, O. et al. The mystery of missing heritability: genetic interactions create phantom heritability. Proc. Natl Acad. Sci. USA 109, 1193–1198 (2012).

  10. 10.

    Escott-Price, V. et al. Polygenic risk score analysis of pathologically confirmed Alzheimer disease. Ann. Neurol. 82, 311–314 (2017).

Download references

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

Affiliations

  1. Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), Institutes of Neurogenetics and Cardiogenetics, University of Lübeck, Lübeck, Germany

    • Lars Bertram
  2. Centre for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway

    • Lars Bertram
  3. McCance Center for Brain Health and Genetics and Aging Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA

    • Rudolph E. Tanzi

Authors

  1. Search for Lars Bertram in:

  2. Search for Rudolph E. Tanzi in:

Competing interests

The authors declare no competing interests.

Corresponding author

Correspondence to Lars Bertram.

About this article

Publication history

Published

DOI

https://doi.org/10.1038/s41582-019-0158-4

Newsletter Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing