CORE
🇺🇦
make metadata, not war
Services
Services overview
Explore all CORE services
Access to raw data
API
Dataset
FastSync
Content discovery
Recommender
Discovery
OAI identifiers
OAI Resolver
Managing content
Dashboard
Bespoke contracts
Consultancy services
Support us
Support us
Membership
Sponsorship
Community governance
Advisory Board
Board of supporters
Research network
About
About us
Our mission
Team
Blog
FAQs
Contact us
research
A genome-wide association study identifies protein quantitative trait loci (pQTLs)
Authors
A Bennett
Aimo Ruokonen
+83 more
AL Dixon
AL Dixon
AL Price
Alison Hurst
AM Dunning
Amanda Bennett
Andrew Singleton
Angela Britton
Anna Murray
Anna-Maria Corsi
Anne B. Newman
B Futcher
B Keavney
B Ketterer
BE Stranger
BE Stranger
C Brunner
CJ Boos
Colin Dayan
D Greenbaum
D Il'yasova
D Reich
David Melzer
Dena Hernandez
DH McDermott
E Boerwinkle
E Gonzalez
EJ Foss
Fulvio Lauretani
G Davey Smith
Giuseppe Paolisso
Greg Tranah
Hana Lango
HG Kraft
HH Goring
I Aird
Ian Rafferty
J Mullberg
J. Raphael Gibbs
Jack Guralnik
Javier Simon-Sanchez
JD Storey
John R. B. Perry
Joyce van de Leemput
JS O'Donnell
Kara Stevens
KW Broman
L Ferrucci
Luigi Ferrucci
M Morley
M Ogorelkova
Marjo-Riitta Jarvelin
Mark I. McCarthy
MF Moffatt
Michael N. Weedon
MN Weedon
MR Jarvelin
Neil Rice
Nicole Washecka
NJ Cox
NJ Timpson
P Rantakallio
P Saravanan
Rongling Li
S Rafiq
S Rafiq
Sajjad Rafiq
Sampath Arepalli
SI Berndt
Sonja Scholz
SP Gygi
SP Yip
Stefania Bandinelli
Tamara Harris
Timothy M. Frayling
TM Frayling
TM Frayling
VG Cheung
Vijay Panicker
Vivian G. Cheung
William Henley
WR Pearson
WS Modi
Publication date
1 January 2008
Publisher
'Public Library of Science (PLoS)'
Doi
Cite
View
on
PubMed
Abstract
There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10 -57), CCL4L1 (p = 3.9×10-21), IL18 (p = 6.8×10-13), LPA (p = 4.4×10-10), GGT1 (p = 1.5×10-7), SHBG (p = 3.1×10-7), CRP (p = 6.4×10-6) and IL1RN (p = 7.3×10-6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10-40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways. © 2008 Melzer et al
Similar works
Full text
Open in the Core reader
Download PDF
Available Versions
Supporting member
Oxford University Research Archive
See this paper in CORE
Go to the repository landing page
Download from data provider
oai:ora.ox.ac.uk:uuid:f50cb3e8...
Last time updated on 30/09/2015
Supporting member
Open Research Exeter
See this paper in CORE
Go to the repository landing page
Download from data provider
oai:ore.exeter.ac.uk:10871/115...
Last time updated on 06/08/2013
Directory of Open Access Journals
See this paper in CORE
Go to the repository landing page
Download from data provider
oai:doaj.org/article:d2f227e9b...
Last time updated on 12/10/2017
Supporting member
Spiral - Imperial College Digital Repository
See this paper in CORE
Go to the repository landing page
Download from data provider
oai:spiral.imperial.ac.uk:1004...
Last time updated on 10/02/2021
Archivio istituzionale della Ricerca - Università degli Studi di Parma
See this paper in CORE
Go to the repository landing page
Download from data provider
oai:air.unipr.it:11381/2865181
Last time updated on 29/10/2019
Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli"
See this paper in CORE
Go to the repository landing page
Download from data provider
oai:iris.unicampania.it:11591/...
Last time updated on 07/05/2019
D-Scholarship@Pitt
See this paper in CORE
Go to the repository landing page
Download from data provider
oai:d-scholarship.pitt.edu:129...
Last time updated on 19/07/2013