Mediation Analysis Demonstrates That Trans-eQTLs Are Often Explained by Cis-Mediation: A Genome-Wide Analysis among 1,800 South Asians

Brandon L. Pierce*, Lin Tong, Lin S. Chen, Ronald Rahaman, Maria Argos, Farzana Jasmine, Shantanu Roy, Rachelle Paul-Brutus, Harm-Jan Westra, Lude Franke, Tonu Esko, Rakibuz Zaman, Tariqul Islam, Mahfuzar Rahman, John A. Baron, Muhammad G. Kibriya, Habibul Ahsan

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

A large fraction of human genes are regulated by genetic variation near the transcribed sequence (cis-eQTL, expression quantitative trait locus), and many cis-eQTLs have implications for human disease. Less is known regarding the effects of genetic variation on expression of distant genes (trans-eQTLs) and their biological mechanisms. In this work, we use genome-wide data on SNPs and array-based expression measures from mononuclear cells obtained from a population-based cohort of 1,799 Bangladeshi individuals to characterize cis- and trans-eQTLs and determine if observed trans-eQTL associations are mediated by expression of transcripts in cis with the SNPs showing trans-association, using Sobel tests of mediation. We observed 434 independent trans-eQTL associations at a false-discovery rate of 0.05, and 189 of these transeQTLs were also cis-eQTLs (enrichment P

Original languageEnglish
Article numbere1004818
Number of pages13
JournalPLoS genetics
Volume10
Issue number12
DOIs
Publication statusPublished - 4-Dec-2014

Keywords

  • GENE-EXPRESSION
  • LOCI
  • ASSOCIATIONS
  • DISEASE
  • RISK

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