ArticleJournal of neurology, neurosurgery, and psychiatry2018
Oligogenic genetic variation of neurodegenerative disease genes in 980 postmortem human brains.
Article in Journal of neurology, neurosurgery, and psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Genetic Variants inInternational journal of molecular sciences · 2025Article
- Incidence of amyotrophic lateral sclerosis-associated genetic variants: a clinic-based study.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Article
- Article
- Pathomechanistic Networks of Motor System Injury in Amyotrophic Lateral Sclerosis.Current neuropharmacology · 2024Review
- Genetic Landscape of Amyotrophic Lateral Sclerosis in Czech Patients.Journal of neuromuscular diseases · 2024Article
- A novel variant inCold Spring Harbor molecular case studies · 2022Review
- Modelling the functional genomics of Parkinson's disease in Caenorhabditis elegans: LRRK2 and beyond.Bioscience reports · 2021Review
- Emerging genetic complexity and rare genetic variants in neurodegenerative brain diseases.Genome medicine · 2021Review
- Novel dominant MPAN family with a complex genetic architecture as a basis for phenotypic variability.Neurology. Genetics · 2020Article
- Genetic perspective on the synergistic connection between vesicular transport, lysosomal and mitochondrial pathways associated with Parkinson's disease pathogenesis.Acta neuropathologica communications · 2020Review
- Genetic modifiers and non-Mendelian aspects of CMT.Brain research · 2020Review
- ALS Genetics, Mechanisms, and Therapeutics: Where Are We Now?Frontiers in neuroscience · 2019Review
- The Role of Genetic Testing in the Clinical Practice and Research of Early-Onset Parkinsonian Disorders in a Hungarian Cohort: Increasing Challenge in Genetic Counselling, Improving Chances in Stratification for Clinical Trials.Frontiers in genetics · 2019Article
- Perspectives on the Genomics of HSP Beyond Mendelian Inheritance.Frontiers in neurology · 2018Review
Corrections and comments
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Authors and funding
17 authors at 8 institutions in 5 countries.
Funding
Abstract
backgroundSeveral studies suggest that multiple rare genetic variants in genes causing monogenic forms of neurodegenerative disorders interact synergistically to increase disease risk or reduce the age of onset, but these studies have not been validated in large sporadic case series.
methodsWe analysed 980 neuropathologically characterised human brains with Alzheimer's disease (AD), Parkinson's disease-dementia with Lewy bodies (PD-DLB), frontotemporal dementia-amyotrophic lateral sclerosis (FTD-ALS) and age-matched controls. Genetic variants were assessed using the American College of Medical Genetics criteria for pathogenicity. Individuals with two or more variants within a relevant disease gene panel were defined as 'oligogenic'.
resultsThe majority of oligogenic variant combinations consisted of a highly penetrant allele or known risk factor in combination with another rare but likely benign allele. The presence of oligogenic variants did not influence the age of onset or disease severity. After controlling for the single known major risk allele, the frequency of oligogenic variants was no different between cases and controls.
conclusionsA priori, individuals with AD, PD-DLB and FTD-ALS are more likely to harbour a known genetic risk factor, and it is the burden of these variants in combination with rare benign alleles that is likely to be responsible for some oligogenic associations. Controlling for this bias is essential in studies investigating a potential role for oligogenic variation in neurodegenerative diseases.
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