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Linkage and association analyses of principal components in expression data
Anthony L Hinrichs1, Robert Culverhouse, Carol H Jin
1Department of Psychiatry, Washington University, 660 South Euclid, Box 8134, St, Louis, Missouri 63110, USA. tony@silver.wustl.edu
BMC Proceedings
|May 10, 2008
Summary
Principal component analysis of gene expression data revealed genetic factors influencing multiple genes on chromosome 14. Two polymorphisms on chromosome 11 were identified as potentially influencing the expression of these linked genes.
Area of Science:
- Genetics
- Genomics
- Bioinformatics
Background:
- Analyzing correlated gene expression data across pedigrees presents challenges.
- Lymphoblastoid cell lines from 194 individuals across 14 Utah CEPH pedigrees were used.
- Multivariate expression phenotypes were derived from six gene sets.
Purpose of the Study:
- To investigate genetic linkage and association for multivariate gene expression phenotypes.
- To identify genetic factors influencing expression of genes linked to chromosome 14.
- To explore the utility of principal component analysis (PCA) for pleiotropic loci.
Main Methods:
- Principal component analysis (PCA) was employed to generate quantitative phenotypes.
- Quantitative genome linkage analysis was performed on third-generation expression traits.
- Association analyses were conducted on first and second-generation pedigree data.
Main Results:
- The strongest linkage signal (LOD score 5.2) was observed for a composite trait of genes linked to chromosome 14.
- Significant linkage signals (LOD > 3.5) were also found on chromosomes 1, 7, 9, and 11.
- Two polymorphisms on chromosome 11 showed significant association with expression traits after multiple testing correction.
Conclusions:
- PCA is a valuable method for analyzing pleiotropic loci.
- Identified single-nucleotide polymorphisms may influence the expression of multiple genes linked to chromosome 14.
- Suggests the presence of additional genetic factors controlling gene expression on various chromosomes.
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