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Screening for Functional Non-coding Genetic Variants Using Electrophoretic Mobility Shift Assay (EMSA) and DNA-affinity Precipitation Assay (DAPA)
Published on: August 21, 2016
Brain expression genome-wide association study (eGWAS) identifies human disease-associated variants
Fanggeng Zou1, High Seng Chai, Curtis S Younkin
1Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Plos Genetics
|June 12, 2012
Summary
Genetic variants influencing brain gene expression are linked to human diseases. This study found significant associations between cisSNPs and transcript levels in brain tissue, highlighting gene expression
Area of Science:
- Neurogenetics
- Genomics
- Molecular Biology
Background:
- Genetic variants can alter brain gene expression, potentially influencing disease risk.
- Understanding these links is crucial for deciphering the genetic basis of neurological and other disorders.
Purpose of the Study:
- To investigate the relationship between genetic variants (cisSNPs) and gene expression levels in human brain tissue.
- To identify cisSNP/transcript associations and assess their enrichment for known disease-associated variants.
Main Methods:
- Expression genome-wide association study (eGWAS) on 24,526 transcripts in cerebellum and temporal cortex from autopsied Alzheimer's disease (AD) and non-AD subjects.
- Analysis of 213,528 cisSNPs within ± 100 kb of transcripts.
- Statistical analysis to identify significant cisSNP/transcript associations (q<0.05).
Main Results:
- Identified 2,980 significant cisSNP/transcript associations in the cerebellum, with 2,089 also significant in the temporal cortex.
- Top cisSNPs showed significant enrichment for human disease-associated variants (2.4-fold).
- Confirmed and identified novel cisSNP/transcript associations for various diseases, including Parkinson's and Alzheimer's.
Conclusions:
- Genetic factors significantly contribute to human brain gene expression across different regions and pathologies.
- Gene expression changes mediated by cisSNPs represent a mechanism underlying various central nervous system (CNS) and non-CNS diseases.
- Integrating expression and disease GWAS enhances the discovery of functionally relevant human disease variants.
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