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

Author

Listed:
  • 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

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 trans-eQTLs were also cis-eQTLs (enrichment P

Suggested Citation

  • 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 Is, 2014. "Mediation Analysis Demonstrates That Trans-eQTLs Are Often Explained by Cis-Mediation: A Genome-Wide Analysis among 1,800 South Asians," PLOS Genetics, Public Library of Science, vol. 10(12), pages 1-13, December.
    • Handle: RePEc:plo:pgen00:1004818
    DOI: 10.1371/journal.pgen.1004818
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    References listed on IDEAS

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    1. Federico Innocenti & Gregory M Cooper & Ian B Stanaway & Eric R Gamazon & Joshua D Smith & Snezana Mirkov & Jacqueline Ramirez & Wanqing Liu & Yvonne S Lin & Cliona Moloney & Shelly Force Aldred & Nat, 2011. "Identification, Replication, and Functional Fine-Mapping of Expression Quantitative Trait Loci in Primary Human Liver Tissue," PLOS Genetics, Public Library of Science, vol. 7(5), pages 1-16, May.
    2. Barbara E Stranger & Stephen B Montgomery & Antigone S Dimas & Leopold Parts & Oliver Stegle & Catherine E Ingle & Magda Sekowska & George Davey Smith & David Evans & Maria Gutierrez-Arcelus & Alkes P, 2012. "Patterns of Cis Regulatory Variation in Diverse Human Populations," PLOS Genetics, Public Library of Science, vol. 8(4), pages 1-13, April.
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