RT Journal Article
SR Electronic
T1 Unraveling the polygenic architecture of complex traits using blood eQTL metaanalysis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 447367
DO 10.1101/447367
A1 Urmo Võsa
A1 Annique Claringbould
A1 Harm-Jan Westra
A1 Marc Jan Bonder
A1 Patrick Deelen
A1 Biao Zeng
A1 Holger Kirsten
A1 Ashis Saha
A1 Roman Kreuzhuber
A1 Silva Kasela
A1 Natalia Pervjakova
A1 Isabel Alvaes
A1 Marie-Julie Fave
A1 Mawusse Agbessi
A1 Mark Christiansen
A1 Rick Jansen
A1 Ilkka Seppälä
A1 Lin Tong
A1 Alexander Teumer
A1 Katharina Schramm
A1 Gibran Hemani
A1 Joost Verlouw
A1 Hanieh Yaghootkar
A1 Reyhan Sönmez
A1 Andrew Brown
A1 Viktorija Kukushkina
A1 Anette Kalnapenkis
A1 Sina Rüeger
A1 Eleonora Porcu
A1 Jaanika Kronberg-Guzman
A1 Johannes Kettunen
A1 Joseph Powell
A1 Bernett Lee
A1 Futao Zhang
A1 Wibowo Arindrarto
A1 Frank Beutner
A1 BIOS Consortium
A1 Harm Brugge
A1 i2QTL Consortium
A1 Julia Dmitreva
A1 Mahmoud Elansary
A1 Benjamin P. Fairfax
A1 Michel Georges
A1 Bastiaan T. Heijmans
A1 Mika Kähönen
A1 Yungil Kim
A1 Julian C. Knight
A1 Peter Kovacs
A1 Knut Krohn
A1 Shuang Li
A1 Markus Loeffler
A1 Urko M. Marigorta
A1 Hailang Mei
A1 Yukihide Momozawa
A1 Martina Müller-Nurasyid
A1 Matthias Nauck
A1 Michel Nivard
A1 Brenda Penninx
A1 Jonathan Pritchard
A1 Olli Raitakari
A1 Olaf Rotzchke
A1 Eline P. Slagboom
A1 Coen D.A. Stehouwer
A1 Michael Stumvoll
A1 Patrick Sullivan
A1 Peter A.C. ‘t Hoen
A1 Joachim Thiery
A1 Anke Tönjes
A1 Jenny van Dongen
A1 Maarten van Iterson
A1 Jan Veldink
A1 Uwe Völker
A1 Cisca Wijmenga
A1 Morris Swertz
A1 Anand Andiappan
A1 Grant W. Montgomery
A1 Samuli Ripatti
A1 Markus Perola
A1 Zoltan Kutalik
A1 Emmanouil Dermitzakis
A1 Sven Bergmann
A1 Timothy Frayling
A1 Joyce van Meurs
A1 Holger Prokisch
A1 Habibul Ahsan
A1 Brandon Pierce
A1 Terho Lehtimäki
A1 Dorret Boomsma
A1 Bruce M. Psaty
A1 Sina A. Gharib
A1 Philip Awadalla
A1 Lili Milani
A1 Willem Ouwehand
A1 Kate Downes
A1 Oliver Stegle
A1 Alexis Battle
A1 Jian Yang
A1 Peter M. Visscher
A1 Markus Scholz
A1 Gregory Gibson
A1 Tõnu Esko
A1 Lude Franke
YR 2018
UL http://biorxiv.org/content/early/2018/10/19/447367.abstract
AB Summary While many disease-associated variants have been identified through genome-wide association studies, their downstream molecular consequences remain unclear.To identify these effects, we performed cis- and trans-expression quantitative trait locus (eQTL) analysis in blood from 31,684 individuals through the eQTLGen Consortium.We observed that cis-eQTLs can be detected for 88% of the studied genes, but that they have a different genetic architecture compared to disease-associated variants, limiting our ability to use cis-eQTLs to pinpoint causal genes within susceptibility loci.In contrast, trans-eQTLs (detected for 37% of 10,317 studied trait-associated variants) were more informative. Multiple unlinked variants, associated to the same complex trait, often converged on trans-genes that are known to play central roles in disease etiology.We observed the same when ascertaining the effect of polygenic scores calculated for 1,263 genome-wide association study (GWAS) traits. Expression levels of 13% of the studied genes correlated with polygenic scores, and many resulting genes are known to drive these traits.