Identifying genetic markers enriched by brain imaging endophenotypes in Alzheimer's disease
Mansu Kim1, Ruiming Wu2, Xiaohui Yao3
1Department of Artificial intelligence, Catholic University of Korea, Bucheon, Republic of Korea.
BMC Medical Genomics
|August 1, 2022
Summary
This study introduces a new method using brain imaging to find genetic variants linked to Alzheimer's disease (AD). The approach significantly improves the detection of AD-related genetic factors compared to traditional methods.
Area of Science:
- Neuroscience
- Genetics
- Medical Imaging
Background:
- Alzheimer's disease (AD) is a leading cause of dementia, characterized by cognitive decline and brain atrophy.
- Heritability estimates for AD range from 60-80%, highlighting the importance of genetic factors.
- Genome-wide association studies (GWAS) have identified over 50 AD susceptibility loci, but imaging genetics offers a novel approach.
Purpose of the Study:
- To develop and validate a novel method for identifying AD genetic variants.
- To leverage imaging endophenotypes to enhance the detection of disease-related genetic markers.
- To improve the specificity of identified genetic markers by linking them to disease outcomes.
Main Methods:
- A three-step linear regression model was employed to map genetic variant effects onto brain imaging traits.
- Diagnostic phenotype effects were mapped onto imaging traits across the brain.
- SNP-diagnosis association was detected by correlating SNP effects with diagnostic effects on brain-wide imaging traits.
Main Results:
- The proposed method successfully identified 41 out of 54 known AD-related susceptibility loci from a smaller cohort.
- Traditional GWAS methods identified only two of these loci in the same cohort.
- The imaging endophenotype-enriched approach demonstrated superior power in detecting AD genetic variants.
Conclusions:
- A novel method for identifying AD genetic variants using brain-wide imaging endophenotypes has been developed.
- This approach enhances detection power and reveals biological pathways from genes to brain traits and AD outcomes.
- The method offers a more effective strategy for discovering genetic determinants of Alzheimer's disease.
Keywords:
Brain imaging geneticsGenome-wide association studyImaging-diagnosis mapImaging-genetics mapMore Related Videos
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