This work was funded by the Louis-Jeantet Foundation (http://www.jeantet.ch/), the European Research Council (Grant ID: 260927 http://erc.europa.eu/), the Swiss National Foundation (Grant ID: 130342 http://www.snf.ch), NCCR Frontiers In Genetics (http://www.frontiers-in-genetics.org), the UK Medical Research Council (http://www.mrc.ac.uk) and the Wellcome Trust (Grant ID: 092731). 

A Boyd

AC Nica

AH Talukder

Alfonso Buil

AR Wood

AS Dimas

BE Stranger

BU Schraml

C Wallace

Christopher David Brown

David M. Evans

DF Conrad

DJ Gaffney

DL Nicolae

DM Greenawalt

Donald F. Conrad

E Grundberg

E Klopocki

EE Schadt

Emmanouil T. Dermitzakis

George Davey Smith

GR Abecasis

H Huang

HJ Westra

J Ding

J Millstein

J Zhu

JD Storey

JE Powell

JK Pickrell

John P. Kemp

Julien Bryois

K Hildner

Karen M. Ho

LA Hindorff

M Gutierrez-Arcelus

M Scutari

Matthew Hurles

ND Miller

NL Barbosa-Morais

Panos Deloukas

RW Jones

SB Montgomery

SJ Loughran

Stephen B. Montgomery

Susan Ring

T Lappalainen

TR Insel

W Wang

Y Li

PLoS Genetics

English

PubMed

Bryois, J

Buil, A

Evans, DM

Kemp, JP

Montgomery, SB

Conrad, DF

Ho, KM

Ring, S

Hurles, M

Deloukas, P

Smith, GD

Dermitzakis, ET

Queen Mary Research Online

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Cis and Trans Effects of Human Genomic Variants on Gene Expression

Bryois Julien

Buil Alfonso

Evans David M.

Kemp John P.

Montgomery Stephen B.

Conrad Donald F.

Ho Karen M.

Ring Susan

Hurles Matthew

Deloukas Panos

Davey Smith George

Dermitzakis Emmanouil T.

Public Library of Science (PLOS)

Gene expression is a heritable cellular phenotype that defines the function of a cell and can lead to diseases in case of misregulation. In order to detect genetic variations affecting gene expression, we performed association analysis of single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) with gene expression measured in 869 lymphoblastoid cell lines of the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort in cis and in trans. We discovered that 3,534 genes (false discovery rate (FDR) = 5%) are affected by an expression quantitative trait locus (eQTL) in cis and 48 genes are affected in trans. We observed that CNVs are more likely to be eQTLs than SNPs. In addition, we found that variants associated to complex traits and diseases are enriched for trans-eQTLs and that trans-eQTLs are enriched for cis-eQTLs. As a variant affecting both a gene in cis and in trans suggests that the cis gene is functionally linked to the trans gene expression, we looked specifically for trans effects of cis-eQTLs. We discovered that 26 cis-eQTLs are associated to 92 genes in trans with the cis-eQTLs of the transcriptions factors BATF3 and HMX2 affecting the most genes. We then explored if the variation of the level of expression of the cis genes were causally affecting the level of expression of the trans genes and discovered several causal relationships between variation in the level of expression of the cis gene and variation of the level of expression of the trans gene. This analysis shows that a large sample size allows the discovery of secondary effects of human variations on gene expression that can be used to construct short directed gene regulatory networks

David M Evans

John P Kemp

Stephen B Montgomery

Donald F Conrad

Karen M Ho

Emmanouil T Dermitzakis

Directory of Open Access Journals

Cis and trans effects of human genomic variants on gene expression.

<div><p>Gene expression is a heritable cellular phenotype that defines the function of a cell and can lead to diseases in case of misregulation. In order to detect genetic variations affecting gene expression, we performed association analysis of single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) with gene expression measured in 869 lymphoblastoid cell lines of the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort in cis and in trans. We discovered that 3,534 genes (false discovery rate (FDR) = 5%) are affected by an expression quantitative trait locus (eQTL) in cis and 48 genes are affected in trans. We observed that CNVs are more likely to be eQTLs than SNPs. In addition, we found that variants associated to complex traits and diseases are enriched for trans-eQTLs and that trans-eQTLs are enriched for cis-eQTLs. As a variant affecting both a gene in cis and in trans suggests that the cis gene is functionally linked to the trans gene expression, we looked specifically for trans effects of cis-eQTLs. We discovered that 26 cis-eQTLs are associated to 92 genes in trans with the cis-eQTLs of the transcriptions factors BATF3 and HMX2 affecting the most genes. We then explored if the variation of the level of expression of the cis genes were causally affecting the level of expression of the trans genes and discovered several causal relationships between variation in the level of expression of the cis gene and variation of the level of expression of the trans gene. This analysis shows that a large sample size allows the discovery of secondary effects of human variations on gene expression that can be used to construct short directed gene regulatory networks.</p></div

Julien Bryois (596234)

Alfonso Buil (29046)

David M. Evans (152874)

John P. Kemp (152856)

Stephen B. Montgomery (159816)

Donald F. Conrad (365590)

Karen M. Ho (596235)

Susan Ring (119324)

Matthew Hurles (56488)

Panos Deloukas (21564)

George Davey Smith (82619)

Emmanouil T. Dermitzakis (120302)

The Francis Crick Institute

Bryois, Julien

Buil, Alfonso

Evans, David M

Kemp, John P

Montgomery, Stephen B

Conrad, Donald F

Ho, Karen M

Ring, Susan

Hurles, Matthew

Deloukas, Panos

Davey Smith, George

Dermitzakis, Emmanouil T

Explore Bristol Research

Buil Demur, Alfonso Alberto

Dermitzakis, Emmanouil

Archive ouverte UNIGE

Cis and trans effects of human genomic variants on gene expression

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https://figshare.com/articles/_Cis_and_Trans_Effects_of_Human_Genomic_Variants_on_Gene_Expression_/1099758

Cis and Trans Effects of Human Genomic Variants on Gene Expression

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