Progress in unraveling the genetic etiology of Parkinson disease in a genomic era
Abstract
Parkinson disease (PD) and Parkinson-plus syndromes are genetically heterogeneous neurological diseases. Initial studies into the genetic causes of PD relied on classical molecular genetic approaches in well-documented case families. More recently, these approaches have been combined with exome sequencing and together have identified 15 causal genes. Additionally, genome-wide association studies (GWASs) have discovered over 25 genetic risk factors. Elucidation of the genetic architecture of sporadic and familial parkinsonism, however, has lagged behind that of simple Mendelian conditions, suggesting the existence of features confounding genetic data interpretation. Here we discuss the successes and potential pitfalls of gene discovery in PD and related disorders in the post-genomic era. With an estimated 30% of trait variance currently unexplained, tackling current limitations will further expedite gene discovery and lead to increased application of these genetic insights in molecular diagnostics using gene panel and exome sequencing strategies.
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About 10-15% of PD cases have familial genetic etiology.
“About 10-15% of PD cases have familial genetic etiology (616).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [616]
PD is characterized by filamentous and oligomeric α-synuclein accumulation and degeneration of dopaminergic neurons in the substantia nigra pars compacta leading to motor impairments.
“It is characterized by filamentous and oligomeric 𝛂 -synuclein ( 𝛂 -syn) accumulation, and degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) leading to motor impairments (357, 616).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [616]
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Blood-Brain Barrier: From Physiology to Disease and Back
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- Authors
- Verstraeten, A., Theuns, J., & Van Broeckhoven, C.
- Affiliations
- University of Antwerp (BE)
- Venue
- Trends in Genetics
- Publisher
- Elsevier BV
- Published
- 2015-03
- Volume
- 31
- Issue
- 3
- Pages
- 140-149
- ISSN
- 0168-9525 (ISSN-L)
- OpenAlex
- W2071536472
- Cited by
- 226
- References
- 5
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 11 · 2023: 19 · 2022: 14 · 2021: 17 · 2020: 24 · 2019: 22 · 2018: 19 · 2017: 29 · 2016: 34 · 2015: 23
- FWCI
- 4.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Genetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- Parkinson's disease, atypical parkinsonism, genetic etiology, causal genes, genetic risk factors, exome sequencing, genome-wide association study, genetic heterogeneity, familial parkinsonism, gene discovery, molecular diagnosis, gene panel
- MeSH terms
- Humans, Mutation, Parkinson Disease, Risk Factors, Genome, Human, Sequence Analysis, DNA, Genetic Predisposition to Disease, Genomics, Genome-Wide Association Study, Exome
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