Oligogenic structure of amyotrophic lateral sclerosis has genetic testing, counselling and therapeutic implications
Our findings represent the first large-scale, case-control assessment of oligogenicity in ALS and show that oligogenic events involving known ALS risk genes are relevant for disease risk in ~6% of ALS but not necessarily for disease onset and survival. This must be considered in genetic counselling and testing by ensuring to use comprehensive gene panels even when a pathogenic variant has already been identified. Moreover, in the age of stratified medication and gene therapy, it supports the need for a complete genetic profile for the correct choice of therapy in all ALS patients.
Authors
- Guy Armand Rouleau (ORCID: https://orcid.org/0000-0001-8403-1418)
- A. Nazlı Başak (ORCID: https://orcid.org/0000-0001-6977-2517)
- Philip Van Damme (ORCID: https://orcid.org/0000-0002-4010-2357)
- Alfredo Iacoangeli (ORCID: https://orcid.org/0000-0002-5280-5017)
- John E. Landers (ORCID: https://orcid.org/0000-0001-8084-5043)
- Philippe Corcia (ORCID: https://orcid.org/0000-0002-1625-8845)
- Vincenzo Silani (ORCID: https://orcid.org/0000-0002-7698-3854)
- Orla M. Hardiman (ORCID: https://orcid.org/0000-0003-2610-1291)
- Allison A. Dilliott (ORCID: https://orcid.org/0000-0003-3863-9304)
- Marc Gotkine (ORCID: https://orcid.org/0000-0003-2541-6232)
- Ammar Al‐Chalabi (ORCID: https://orcid.org/0000-0002-4924-7712)
- Mamede de Carvalho (ORCID: https://orcid.org/0000-0001-7556-0158)
- Johnathan Cooper‐Knock (ORCID: https://orcid.org/0000-0002-0873-8689)
- Russell Lewis McLaughlin (ORCID: https://orcid.org/0000-0003-3915-2135)
- Nicola Ticozzi (ORCID: https://orcid.org/0000-0001-5963-7426)
- Sali M.K. Farhan (ORCID: https://orcid.org/0000-0001-5936-0957)
- Philippe Couratier (ORCID: https://orcid.org/0000-0001-9562-856X)
- Yosef M Lerner
- Christopher E. Shaw (ORCID: https://orcid.org/0000-0003-0251-0146)
- Richard Dobson (ORCID: https://orcid.org/0000-0003-4224-9245)
- Susana Pinto (ORCID: https://orcid.org/0000-0002-0727-5897)
- Jan H. Veldink (ORCID: https://orcid.org/0000-0001-5572-9657)
- Patrick Vourc’h (ORCID: https://orcid.org/0000-0001-7960-8139)
- Jonathan D. Glass (ORCID: https://orcid.org/0000-0002-3295-4971)
- Pamela J. Shaw (ORCID: https://orcid.org/0000-0002-8925-2567)
- Karen Morrison (ORCID: https://orcid.org/0000-0003-0216-5717)
- Ahmad Al Khleifat (ORCID: https://orcid.org/0000-0002-7406-9831)
- Peter M. Andersen (ORCID: https://orcid.org/0000-0003-0094-5429)
- Mónica Povedano (ORCID: https://orcid.org/0000-0002-7991-669X)
- Markus Weber
- Leonard H. van den Berg
- Jesús S. Mora Pardina
- Vivian E. Drory
Institutions
- Université de Tours (FR)
- Queen's University Belfast (GB)
- Montreal Neurological Institute and Hospital (CA)
- Koç University (TR)
- University of Lisbon (PT)
- Emory University (US)
- Inserm (FR)
- Tel Aviv University (IL)
- University of Massachusetts Chan Medical School (US)
- King's College London (GB)
- University of Milan (IT)
- Hebrew University of Jerusalem (IL)
- South London and Maudsley NHS Foundation Trust (GB)
- Trinity College Dublin (IE)
- Tel Aviv Sourasky Medical Center (IL)
- Kantonsspital St. Gallen (CH)
- Hadassah Medical Center (IL)
- Bellvitge University Hospital (ES)
- University Medical Center Utrecht (NL)
- Centre Hospitalier Universitaire de Tours (FR)
- Centre Hospitalier Universitaire de Limoges (FR)
- IRCCS Istituto Auxologico Italiano (IT)
- Perron Institute for Neurological and Translational Science (AU)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- King's College Hospital (GB)
- VIB-KU Leuven Center for Brain & Disease Research (BE)
- Hospital Universitario San Rafael (ES)
- McGill University (CA)
- Université de Limoges (FR)
- Umeå University (SE)
- University of Sheffield (GB)
- KU Leuven (BE)
Publication Details
- Journal
- Journal of Neurology Neurosurgery & Psychiatry
- Published
- 2025-02-13
- DOI
- https://doi.org/10.1136/jnnp-2024-335364
- Citations
- 10
- Primary Topic
- Amyotrophic Lateral Sclerosis Research
- Type
- article
- Field-Weighted Citation Impact
- 13.89
Funders
- Michael J. Fox Foundation for Parkinson's Research
- ALS Association
- ALS Society of Canada
- South London and Maudsley NHS Foundation Trust
- Fondation Brain Canada
- Wellcome Trust
- MND Scotland
- Scottish Government
- Maudsley Charity
- EU Joint Programme – Neurodegenerative Disease Research
- Spastic Paraplegia Foundation
- National Institute for Health and Care Research
- British Heart Foundation
- Department of Health and Social Care
- Motor Neurone Disease Association
- Rosetrees Trust
- Public Health Agency
- Alzheimer’s Research UK
- Horizon 2020 Framework Programme
- Chief Scientist Office, Scottish Government Health and Social Care Directorate
- Montreal Neurological Institute and Hospital
- Medical Research Council
- Engineering and Physical Sciences Research Council
- Economic and Social Research Council
- Menzies Centre for Australian Studies, King's College London, University of London
- Health and Social Care Research and Development Division