Abstract
Background: Amyotrophic lateral sclerosis (ALS), Alzheimer's, and Parkinson's diseases are age-related neurodegenerative diseases. ALS is not a single entity but a syndrome with many different causes. In all 3 diseases, gene mutations account for only 10-15% of cases. Many environmental and lifestyle factors have been implicated as risk factors for ALS, though none have been proven to cause the disease. It is generally believed that ALS results from interactions between environmental risk factors and genetic predisposing factors. The advent of next-generation sequencing and recent advances in research into environmental risk factors offer the opportunity to investigate these interactions. Summary: We propose a hypothesis to explain the syndrome of ALS based on the interaction of many individual environmental risk factors with many individual genetic predisposing factors. We hypothesize that there are many such combinations of individual, specific, genetic, and environmental factors, and that each combination can lead to the development of the syndrome of ALS. We also propose a hypothesis that explains the overlap between the age-related neurodegenerations and their genetic underpinnings. Age and duration of exposure are crucial factors in these age-related neurodegenerative diseases, and we consider how these may relate to gene-environment interactions. Key Messages: To date, genetic studies and environmental studies have investigated the causes of ALS separately. We argue that this univariate approach will not lead to discoveries of important gene-environment interactions. We propose new research approaches to investigating gene-environment interactions based on these hypotheses.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 261-267 |
| Number of pages | 7 |
| Journal | Annals of Neurosciences |
| DOIs | |
| State | Accepted/In press - Jan 1 2018 |
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Keywords
- Amyotrophic lateral sclerosis
- Environmental risk factors
- Gene-environment-time interactions
- Genetic predisposition
- Neurodegenerative diseases
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Gene-Environment-Time Interactions in Neurodegenerative Diseases : Hypotheses and Research Approaches. / Bradley, Walter G; Andrew, Angeline S.; Traynor, Bryan J.; Chiò, Adriano; Butt, Tanya H.; Stommel, Elijah W.
In: Annals of Neurosciences, 01.01.2018, p. 261-267.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Gene-Environment-Time Interactions in Neurodegenerative Diseases
T2 - Hypotheses and Research Approaches
AU - Bradley, Walter G
AU - Andrew, Angeline S.
AU - Traynor, Bryan J.
AU - Chiò, Adriano
AU - Butt, Tanya H.
AU - Stommel, Elijah W.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Background: Amyotrophic lateral sclerosis (ALS), Alzheimer's, and Parkinson's diseases are age-related neurodegenerative diseases. ALS is not a single entity but a syndrome with many different causes. In all 3 diseases, gene mutations account for only 10-15% of cases. Many environmental and lifestyle factors have been implicated as risk factors for ALS, though none have been proven to cause the disease. It is generally believed that ALS results from interactions between environmental risk factors and genetic predisposing factors. The advent of next-generation sequencing and recent advances in research into environmental risk factors offer the opportunity to investigate these interactions. Summary: We propose a hypothesis to explain the syndrome of ALS based on the interaction of many individual environmental risk factors with many individual genetic predisposing factors. We hypothesize that there are many such combinations of individual, specific, genetic, and environmental factors, and that each combination can lead to the development of the syndrome of ALS. We also propose a hypothesis that explains the overlap between the age-related neurodegenerations and their genetic underpinnings. Age and duration of exposure are crucial factors in these age-related neurodegenerative diseases, and we consider how these may relate to gene-environment interactions. Key Messages: To date, genetic studies and environmental studies have investigated the causes of ALS separately. We argue that this univariate approach will not lead to discoveries of important gene-environment interactions. We propose new research approaches to investigating gene-environment interactions based on these hypotheses.
AB - Background: Amyotrophic lateral sclerosis (ALS), Alzheimer's, and Parkinson's diseases are age-related neurodegenerative diseases. ALS is not a single entity but a syndrome with many different causes. In all 3 diseases, gene mutations account for only 10-15% of cases. Many environmental and lifestyle factors have been implicated as risk factors for ALS, though none have been proven to cause the disease. It is generally believed that ALS results from interactions between environmental risk factors and genetic predisposing factors. The advent of next-generation sequencing and recent advances in research into environmental risk factors offer the opportunity to investigate these interactions. Summary: We propose a hypothesis to explain the syndrome of ALS based on the interaction of many individual environmental risk factors with many individual genetic predisposing factors. We hypothesize that there are many such combinations of individual, specific, genetic, and environmental factors, and that each combination can lead to the development of the syndrome of ALS. We also propose a hypothesis that explains the overlap between the age-related neurodegenerations and their genetic underpinnings. Age and duration of exposure are crucial factors in these age-related neurodegenerative diseases, and we consider how these may relate to gene-environment interactions. Key Messages: To date, genetic studies and environmental studies have investigated the causes of ALS separately. We argue that this univariate approach will not lead to discoveries of important gene-environment interactions. We propose new research approaches to investigating gene-environment interactions based on these hypotheses.
KW - Amyotrophic lateral sclerosis
KW - Environmental risk factors
KW - Gene-environment-time interactions
KW - Genetic predisposition
KW - Neurodegenerative diseases
UR - http://www.scopus.com/inward/record.url?scp=85058183781&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85058183781&partnerID=8YFLogxK
U2 - 10.1159/000495321
DO - 10.1159/000495321
M3 - Article
AN - SCOPUS:85058183781
SP - 261
EP - 267
JO - Annals of Neurosciences
JF - Annals of Neurosciences
SN - 0972-7531
ER -