期刊
NPJ GENOMIC MEDICINE
卷 7, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41525-021-00267-9
关键词
-
资金
- MND Association
- Wellcome Trust
- Medical Research Council at the Centre for Integrated Genomic Medical Research, University of Manchester
- Maudsley Charity [980]
- Guy's & St. Thomas' Charity [TR130505]
- UK Medical Research Council
- Engineering and Physical Sciences Research Council
- Economic and Social Research Council
- Department of Health and Social Care (England)
- Chief Scientist Office of the Scottish Government Health and Social Care Directorates
- Health and Social Care Research and Development Division (Welsh Government)
- Public Health Agency (Northern Ireland)
- British Heart Foundation
- Motor Neurone Disease Association (MNDA)
- NIHR Maudsley Biomedical Research Centre
- ALS Association Milton Safenowitz Research Fellowship
- United Kingdom, Medical Research Council [MR/L501529/1, MR/R024804/1]
- Economic and Social Research Council [ES/L008238/1]
- European Community's Health Seventh Framework Program (FP7/2007-2013) [259867]
- Horizon 2020 Program (H2020-PHC-2014-two-stage) [633413]
- European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme [772376 -EScORIAL]
- IWT
- Belgian ALS Liga
- Opening the Future Fund (KU Leuven)
- E. von Behring Chair for Neuromuscular and Neurodegenerative Disorders
- ALS Liga Belgie
- KU Leuven funds Een Hart voor ALS
- Laeversfonds voor ALS Onderzoek
- Valery Perrier Race against ALS Fund
- US ALS Association
- US National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (NINDS) [R01NS073873]
- American ALS Association
There is a strong genetic contribution to the risk of Amyotrophic lateral sclerosis (ALS), with heritability estimates of up to 60%. Variants in ALS genes, including repeat expansion in C9orf72, inversion in VCP, and insertion in ERBB4, have been identified as associated with ALS risk and specific disease phenotypes.
There is a strong genetic contribution to Amyotrophic lateral sclerosis (ALS) risk, with heritability estimates of up to 60%. Both Mendelian and small effect variants have been identified, but in common with other conditions, such variants only explain a little of the heritability. Genomic structural variation might account for some of this otherwise unexplained heritability. We therefore investigated association between structural variation in a set of 25 ALS genes, and ALS risk and phenotype. As expected, the repeat expansion in the C9orf72 gene was identified as associated with ALS. Two other ALS-associated structural variants were identified: inversion in the VCP gene and insertion in the ERBB4 gene. All three variants were associated both with increased risk of ALS and specific phenotypic patterns of disease expression. More than 70% of people with respiratory onset ALS harboured ERBB4 insertion compared with 25% of the general population, suggesting respiratory onset ALS may be a distinct genetic subtype.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据