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Research paper
An estimate of amyotrophic lateral sclerosis heritability using twin data
  1. A Al-Chalabi1,
  2. F Fang2,
  3. M F Hanby1,
  4. P N Leigh1,
  5. C E Shaw1,
  6. W Ye2,
  7. F Rijsdijk3
  1. 1King's College London, MRC Centre for Neurodegeneration Research, Institute of Psychiatry, London, UK
  2. 2Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  3. 3MRC Centre for Social, Genetic and Developmental Psychiatry, NIHR Biomedical Research Centre for Mental Health, King's College London, London, UK
  1. Correspondence to Professor Ammar Al-Chalabi, MRC Centre for Neurodegeneration Research, P 041, Institute of Psychiatry, King's College London, London SE5 8AF, UK; ammar.al-chalabi{at}kcl.ac.uk

Abstract

Background Causative gene mutations have been identified in about 2% of those with amyotrophic lateral sclerosis (ALS), often, but not always, when there is a strong family history. There is an assumption that there is a genetic component to all ALS, but genome-wide association studies have yet to produce a robustly replicated result. A definitive estimate of ALS heritability is therefore required to determine whether ongoing efforts to find susceptibility genes are worth while.

Methods The authors performed two twin studies, one population- and one clinic-based. The authors used structural equation modelling to perform a meta-analysis of data from these studies and an existing twin study to estimate ALS heritability, and identified 171 twin pairs in which at least one twin had ALS.

Results and discussion Five monozygotic twin pairs were concordant-affected, and 44 discordant-affected. No dizygotic twin pairs were concordant-affected, and 122 discordant-affected. The heritability of sporadic ALS was estimated as 0.61 (0.38 to 0.78) with the unshared environmental component 0.39 (0.22 to 0.62). ALS has a high heritability, and efforts to find causative genes should continue.

  • Twin study
  • amyotrophic lateral sclerosis
  • genetics
  • heritability
  • frontotemporal dementia
  • ALS
  • genetics
  • motor neuron disease

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

https://doi.org/10.1136/jnnp.2010.207464

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    Footnotes

    • Linked articles 224816.

    • Funding FF and WY were supported by Bjorklunds Fond 2008-20892. MFH was supported by the British Geriatric Society. We thank the Medical Research Council (UK), the Wellcome Trust, the Motor Neurone Disease Association of Great Britain and Northern Ireland, The American ALS Association, the ALS Therapy Alliance and the Angel Fund for support.

    • Competing interests None.

    • Patient consent Obtained.

    • Ethics approval Ethics approval was provided by the King's College Hospital and SLAM/IOP Research Ethics Committees for the UK participants. For the Swedish Twin Registry, the ethical advice from the Research Ethics Committee of the Karolinska Institutet was that specific approval was not required to use the data. For the British MND Twin Study (1997) we used published data.

    • Provenance and peer review Not commissioned; externally peer reviewed.

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