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

doi:10.1371/journal.pgen.1004818

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

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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 language	English
Article number	e1004818
Number of pages	13
Journal	PLoS genetics
Volume	10
Issue number	12
DOIs	https://doi.org/10.1371/journal.pgen.1004818
Publication status	Published - 4-Dec-2014

Keywords

GENE-EXPRESSION
LOCI
ASSOCIATIONS
DISEASE
RISK

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Mediation Analysis Demonstrates That Trans-eQTLs Are Often Explained by Cis-Mediation: A Genome-Wide Analysis among 1,800 South AsiansFinal publisher's version, 994 KBLicence: CC BY

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Data from: Mediation analysis demonstrates that trans-eQTLs are often explained by cis-mediation: a genome-wide analysis among 1,800 South Asians
Pierce, B. L. (Creator), Tong, L. (Creator), Chen, L. S. (Creator), Rahaman, R. (Creator), Argos, M. (Creator), Jasmine, F. (Creator), Roy, S. (Creator), Paul-Brutus, R. (Creator), Westra, H. J. (Creator), Franke, L. (Creator), Esko, T. (Creator), Zaman, R. (Creator), Islam, T. (Creator), Rahman, M. (Creator), Baron, J. A. (Creator), Kibriya, M. G. (Creator) & Ahsan, H. (Creator), University of Groningen, 12-Dec-2014
DOI: 10.5061/dryad.tp097
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Pierce, B. L., Tong, L., Chen, L. S., Rahaman, R., Argos, M., Jasmine, F., Roy, S., Paul-Brutus, R., Westra, H.-J., Franke, L., Esko, T., Zaman, R., Islam, T., Rahman, M., Baron, J. A., Kibriya, M. G., & Ahsan, H. (2014). Mediation Analysis Demonstrates That Trans-eQTLs Are Often Explained by Cis-Mediation: A Genome-Wide Analysis among 1,800 South Asians. PLoS genetics, 10(12), Article e1004818. https://doi.org/10.1371/journal.pgen.1004818

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

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",

keywords = "GENE-EXPRESSION, LOCI, ASSOCIATIONS, DISEASE, RISK",

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

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Pierce, BL, Tong, L, Chen, LS, Rahaman, R, Argos, M, Jasmine, F, Roy, S, Paul-Brutus, R, Westra, H-J , Franke, L, Esko, T, Zaman, R, Islam, T, Rahman, M, Baron, JA, Kibriya, MG & Ahsan, H 2014, 'Mediation Analysis Demonstrates That Trans-eQTLs Are Often Explained by Cis-Mediation: A Genome-Wide Analysis among 1,800 South Asians', PLoS genetics, vol. 10, no. 12, e1004818. https://doi.org/10.1371/journal.pgen.1004818

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AU - Pierce, Brandon L.

AU - Tong, Lin

AU - Chen, Lin S.

AU - Rahaman, Ronald

AU - Argos, Maria

AU - Jasmine, Farzana

AU - Roy, Shantanu

AU - Paul-Brutus, Rachelle

AU - Westra, Harm-Jan

AU - Franke, Lude

AU - Esko, Tonu

AU - Zaman, Rakibuz

AU - Islam, Tariqul

AU - Rahman, Mahfuzar

AU - Baron, John A.

AU - Kibriya, Muhammad G.

AU - Ahsan, Habibul

PY - 2014/12/4

Y1 - 2014/12/4

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AB - 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

KW - GENE-EXPRESSION

KW - LOCI

KW - ASSOCIATIONS

KW - DISEASE

KW - RISK

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DO - 10.1371/journal.pgen.1004818

M3 - Article

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JO - PLoS genetics

JF - PLoS genetics

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M1 - e1004818

ER -

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

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Data from: Mediation analysis demonstrates that trans-eQTLs are often explained by cis-mediation: a genome-wide analysis among 1,800 South Asians

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