News & Views | Published:

Motor neuron disease

Common genetic variants and the heritability of ALS

Nature Reviews Neurology volume 10, pages 549550 (2014) | Download Citation

Amyotrophic lateral sclerosis (ALS) shows complex inheritance. A new meta-analysis of three data sets has replicated previous estimates of the heritability attributable to common genetic variation, corroborated some previously identified disease-associated genetic loci, and suggested novel loci. Despite such efforts, our understanding of the genetic architecture of ALS remains limited.

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.

    et al. Genome-wide analysis of the heritability of amyotrophic lateral sclerosis. JAMA Neurol. .

  2. 2.

    , , & GCTA: a tool for genome-wide complex trait analysis. Am. J. Hum. Genet. 88, 76–82 (2011).

  3. 3.

    et al. The risk to relatives of patients with sporadic amyotrophic lateral sclerosis. Brain 134, 3454–3457 (2011).

  4. 4.

    et al. An estimate of amyotrophic lateral sclerosis heritability using twin data. J. Neurol. Neurosurg. Psychiatry 81, 1324–1326 (2010).

  5. 5.

    , , , & The heritability of amyotrophic lateral sclerosis in a clinically ascertained United States research registry. PLoS ONE 6, e27985 (2011).

  6. 6.

    et al. A genome-wide association meta-analysis identifies a novel locus at 17q11.2 associated with sporadic amyotrophic lateral sclerosis. Hum. Mol. Genet. 23, 2220–2231 (2014).

  7. 7.

    et al. Amyotrophic lateral sclerosis associated with homozygosity for an Asp90Ala mutation in CuZn-superoxide dismutase. Nat. Genet. 10, 61–66 (1995).

  8. 8.

    et al. Evidence for an oligogenic basis of amyotrophic lateral sclerosis. Hum. Mol. Genet. 21, 3776–3784 (2012).

  9. 9.

    & Modelling the effects of penetrance and family size on rates of sporadic and familial disease. Hum. Hered. 71, 281–288 (2011).

  10. 10.

    et al. Proposed criteria for familial amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. 12, 157–159 (2011).

Download references

Acknowledgements

A.A.-C. is involved in an EU Joint Programme–Neurodegenerative Disease Research (JPND) project, which is supported by the Medical Research Council and Economic and Social Research Council under the aegis of JPND. A.A.-C. receives salary support from the National Institute for Health Research (NIHR) Dementia Biomedical Research Unit at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The work leading up to this publication was funded by the European Community's Health Seventh Framework Programme (FP7/2007–2013; grant agreement number 259867). P.M.V. receives financial support from the Australian National Health and Medical Research Council.

Author information

Affiliations

  1. Institute of Psychiatry, Psychology and Neuroscience, Department of Basic and Clinical Neuroscience, King's College London, London SE5 8AF, UK.

    • Ammar Al-Chalabi
  2. Queensland Brain Institute, University of Queensland, QBI Building (#79), St Lucia, Brisbane, Qld 4072, Australia.

    • Peter M. Visscher

Authors

  1. Search for Ammar Al-Chalabi in:

  2. Search for Peter M. Visscher in:

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Ammar Al-Chalabi.

About this article

Publication history

Published

DOI

https://doi.org/10.1038/nrneurol.2014.166

Further reading

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