Copyright © 2008 The American Society of Human Genetics. All rights reserved.
The American Journal of Human Genetics, Volume 82, Issue 5, 1101-1113, 24 April 2008
doi:10.1016/j.ajhg.2008.03.006
Article
Genetic Architecture of Transcript-Level Variation in Humans
Shiwei Duan1, R. Stephanie Huang1, Wei Zhang1, Wasim K. Bleibel1, Cheryl A. Roe2, Tyson A. Clark3, Tina X. Chen3, Anthony C. Schweitzer3, John E. Blume3, Nancy J. Cox2 and M. Eileen Dolan1, 
, 
1 Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA
2 Section of Genetic Medicine, Departments of Medicine and Human Genetics, University of Chicago, Chicago, IL 60637, USA
3 Expression Research, Affymetrix Laboratory, Affymetrix Inc., Santa Clara, CA 95051, USA
Corresponding authorAbstract
We report here the results of testing the pairwise association of 12,747 transcriptional gene-expression values with more than two million single-nucleotide polymorphisms (SNPs) in samples of European (CEPH from Utah; CEU) and African (Yoruba from Ibadan; YRI) ancestry. We found 4,677 and 5,125 significant associations between expression quantitative nucleotides (eQTNs) and transcript clusters in the CEU and the YRI samples, respectively. The physical distance between an eQTN and its associated transcript cluster was referred to as the intrapair distance. An association with 4 Mb or less intrapair distance was defined as local; otherwise, it was defined as distant. The enrichment analysis of functional categories shows that genes harboring the local eQTNs are enriched in the categories related to nucleosome and chromatin assembly; the genes harboring the distant eQTNs are enriched in the categories related to transmembrane signal transduction, suggesting that these biological pathways are likely to play a significant role in regulation of gene expression. We highlight in the EPHX1 gene a deleterious nonsynonymous SNP that is distantly associated with gene expression of ORMDL3, a susceptibility gene for asthma.
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