Unraveling the polygenic architecture of complex traits using blood eQTL metaanalysis
Author:
Võsa UrmoORCID, Claringbould AnniqueORCID, Westra Harm-Jan, Bonder Marc Jan, Deelen Patrick, Zeng Biao, Kirsten Holger, Saha Ashis, Kreuzhuber Roman, Kasela Silva, Pervjakova Natalia, Alvaes Isabel, Fave Marie-Julie, Agbessi Mawusse, Christiansen Mark, Jansen Rick, Seppälä Ilkka, Tong Lin, Teumer Alexander, Schramm Katharina, Hemani Gibran, Verlouw Joost, Yaghootkar Hanieh, Sönmez Reyhan, Brown Andrew, Kukushkina Viktorija, Kalnapenkis Anette, Rüeger Sina, Porcu Eleonora, Kronberg-Guzman Jaanika, Kettunen Johannes, Powell Joseph, Lee Bernett, Zhang Futao, Arindrarto Wibowo, Beutner Frank, Brugge Harm, Dmitreva Julia, Elansary Mahmoud, Fairfax Benjamin P., Georges Michel, Heijmans Bastiaan T., Kähönen Mika, Kim Yungil, Knight Julian C., Kovacs Peter, Krohn Knut, Li Shuang, Loeffler Markus, Marigorta Urko M., Mei Hailang, Momozawa Yukihide, Müller-Nurasyid Martina, Nauck Matthias, Nivard Michel, Penninx Brenda, Pritchard Jonathan, Raitakari Olli, Rotzchke Olaf, Slagboom Eline P., Stehouwer Coen D.A., Stumvoll Michael, Sullivan Patrick, Hoen Peter A.C. ‘t, Thiery Joachim, Tönjes Anke, van Dongen Jenny, van Iterson Maarten, Veldink Jan, Völker Uwe, Wijmenga Cisca, Swertz Morris, Andiappan Anand, Montgomery Grant W., Ripatti Samuli, Perola Markus, Kutalik Zoltan, Dermitzakis Emmanouil, Bergmann Sven, Frayling Timothy, van Meurs Joyce, Prokisch Holger, Ahsan Habibul, Pierce Brandon, Lehtimäki Terho, Boomsma Dorret, Psaty Bruce M., Gharib Sina A., Awadalla Philip, Milani Lili, Ouwehand Willem, Downes Kate, Stegle Oliver, Battle Alexis, Yang Jian, Visscher Peter M., Scholz Markus, Gibson Gregory, Esko Tõnu, Franke LudeORCID, ,
Abstract
SummaryWhile many disease-associated variants have been identified through genome-wide association studies, their downstream molecular consequences remain unclear.To identify these effects, we performedcis-andtrans-expressionquantitative trait locus (eQTL) analysis in blood from 31,684 individuals through the eQTLGen Consortium.We observed thatcis-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 usecis-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.
Publisher
Cold Spring Harbor Laboratory
Cited by
280 articles.
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