Genetic Architecture of Transcript-Level Variation in Humans

Shiwei Duan, R. Stephanie Huang, Wei Zhang, Wasim K. Bleibel, Cheryl A. Roe, Tyson A. Clark, Tina X. Chen, Anthony C. Schweitzer, John E. Blume, Nancy J. Cox, M. Eileen Dolan

Research output: Contribution to journalArticlepeer-review

113 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1101-1113
Number of pages13
JournalAmerican Journal of Human Genetics
Issue number5
StatePublished - May 9 2008

Bibliographical note

Funding Information:
We thank the International HapMap Consortium for data availability and Jeong-Ah Kang for maintaining cell lines. This Pharmacogenetics of Anticancer Agents Research (PAAR) Group study was supported by National Institutes of Health/National Institute of General Medical Sciences grant U01GM61393. PAAR data have been deposited into PharmGKB, a knowledge base supported by U01GM61374. Gene-expression data are deposited in Gene Expression Omnibus: GSE7851. Four authors of this manuscript (T.A.C., T.X.C., A.C.S., and J.E.B.) are employees of Affymetrix Inc., Santa Clara, CA 95051. Their employment with Affymetrix could be construed as a conflict of interest because they may indirectly benefit from sales of Affymetrix GeneChip Human Exon 1.0 ST array.


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