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A genome-wide association study of global gene expression
 

Summary: A genome-wide association study of global
gene expression
Anna L Dixon1,2,6, Liming Liang3,6, Miriam F Moffatt1,6, Wei Chen3, Simon Heath4, Kenny C C Wong1,
Jenny Taylor2, Edward Burnett5, Ivo Gut4, Martin Farrall2, G Mark Lathrop4, Gonc¸alo R Abecasis3 &
William O C Cookson1
We have created a global map of the effects of polymorphism on gene expression in 400 children from families recruited through
a proband with asthma. We genotyped 408,273 SNPs and identified expression quantitative trait loci from measurements of
54,675 transcripts representing 20,599 genes in Epstein-Barr virus­transformed lymphoblastoid cell lines. We found that 15,084
transcripts (28%) representing 6,660 genes had narrow-sense heritabilities (H2) 4 0.3. We executed genome-wide association
scans for these traits and found peak lod scores between 3.68 and 59.1. The most highly heritable traits were markedly enriched
in Gene Ontology descriptors for response to unfolded protein (chaperonins and heat shock proteins), regulation of progression
through the cell cycle, RNA processing, DNA repair, immune responses and apoptosis. SNPs that regulate expression of these
genes are candidates in the study of degenerative diseases, malignancy, infection and inflammation. We have created a
downloadable database to facilitate use of our findings in the mapping of complex disease loci.
Variation in gene transcription is important in mediating disease
susceptibility, and global identification of genetic variants that regulate
gene transcription will be helpful in mapping human disease genes.
The many genome-wide association (GWA) studies currently under-
way are likely to identify multiple genetic variants that are associated
with multifactorial traits. We anticipate that these variants will often

  

Source: Abecasis, Goncalo - Department of Biostatistics, University of Michigan

 

Collections: Biology and Medicine; Mathematics