Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Dokumenter

  • Andrew A. Brown
  • Juan J. Fernandez-Tajes
  • Mun gwan Hong
  • Caroline A. Brorsson
  • Robert W. Koivula
  • David Davtian
  • Théo Dupuis
  • Ambra Sartori
  • Theodora Dafni Michalettou
  • Ian M. Forgie
  • Jonathan Adam
  • Kristine H. Allin
  • Robert Caiazzo
  • Henna Cederberg
  • Federico De Masi
  • Petra J.M. Elders
  • Giuseppe N. Giordano
  • Mark Haid
  • Tue H. Hansen
  • Andrew T. Hattersley
  • Alison J. Heggie
  • Cédric Howald
  • Angus G. Jones
  • Tarja Kokkola
  • Markku Laakso
  • Anubha Mahajan
  • Andrea Mari
  • Timothy J. McDonald
  • Donna McEvoy
  • Miranda Mourby
  • Petra B. Musholt
  • Birgitte Nilsson
  • Francois Pattou
  • Deborah Penet
  • Violeta Raverdy
  • Martin Ridderstråle
  • Luciana Romano
  • Femke Rutters
  • Sapna Sharma
  • Harriet Teare
  • Leen ‘t Hart
  • Jagadish Vangipurapu
  • Paul W. Franks
  • Gary Frost
  • Harald Grallert
  • Bernd Jablonka
  • Mark I. McCarthy
  • Imre Pavo
  • Hartmut Ruetten
  • Mark Walker
  • Kofi Adragni
  • Rosa Lundbye L. Allesøe
  • Anna A. Artati
  • Naeimeh Atabaki-Pasdar
  • Tania Baltauss
  • Anna L. Barnett
  • Patrick Baum
  • Jimmy D. Bell
  • Joline W. Beulens
  • Susanna B. Bianzano
  • Roberto Bizzotto
  • Amelie Bonnefond
  • Louise Cabrelli
  • Matilda Dale
  • Adem Y. Dawed
  • Nathalie de Preville
  • Koen F. Dekkers
  • Harshal A. Deshmukh
  • Christiane Dings
  • Louise Donnelly
  • Avirup Dutta
  • Beate Ehrhardt
  • Rebeca Eriksen
  • Jorge Ferrer
  • Hugo Fitipaldi
  • Annemette Forman
  • Andreas Fritsche
  • Philippe Froguel
  • Johann Gassenhuber
  • Stephen Gough
  • Ulrike Graefe-Mody
  • Rolf Grempler
  • Lenka Groeneveld
  • Leif Groop
  • Valborg Gudmundsdóttir
  • Ramneek Gupta
  • Anita M.H. Hennige
  • Anita V. Hill
  • Reinhard W. Holl
  • Michelle Hudson
  • Christopher Jennison
  • Jane Kaye
  • Gwen Kennedy
  • Maria Klintenberg
  • Teemu Kuulasmaa
  • Thorsten Lehr
  • Heather Loftus
  • Gianluca Mazzoni
  • Nicky McRobert
  • Ian McVittie
  • Rachel Nice
  • Claudia Nicolay
  • Giel Nijpels
  • Colin N. Palmer
  • Helle K. Pedersen
  • Mandy H. Perry
  • Hugo Pomares-Millan
  • Cornelia P. Prehn
  • Anna Ramisch
  • Neil Robertson
  • Marianne Rodriquez
  • Peter Sackett
  • Nina Scherer
  • Nisha Shah
  • Iryna Sihinevich
  • Roderick C. Slieker
  • Nadja B. Sondertoft
  • Birgit Steckel-Hamann
  • Melissa K. Thomas
  • Elizabeth Louise L. Thomas
  • Barbara Thorand
  • Claire E. Thorne
  • Joachim Tillner
  • Andrea Tura
  • Mathias Uhlen
  • Nienke van Leeuwen
  • Sabine van Oort
  • Helene Verkindt
  • Josef Vogt
  • Peter W. Wad Sackett
  • Agata Wesolowska-Andersen
  • Brandon Whitcher
  • Margaret W. White
  • Jerzy Adamski
  • Jochen M. Schwenk
  • Ewan R. Pearson
  • Emmanouil T. Dermitzakis
  • Ana Viñuela

We evaluate the shared genetic regulation of mRNA molecules, proteins and metabolites derived from whole blood from 3029 human donors. We find abundant allelic heterogeneity, where multiple variants regulate a particular molecular phenotype, and pleiotropy, where a single variant associates with multiple molecular phenotypes over multiple genomic regions. The highest proportion of share genetic regulation is detected between gene expression and proteins (66.6%), with a further median shared genetic associations across 49 different tissues of 78.3% and 62.4% between plasma proteins and gene expression. We represent the genetic and molecular associations in networks including 2828 known GWAS variants, showing that GWAS variants are more often connected to gene expression in trans than other molecular phenotypes in the network. Our work provides a roadmap to understanding molecular networks and deriving the underlying mechanism of action of GWAS variants using different molecular phenotypes in an accessible tissue.

OriginalsprogEngelsk
Artikelnummer5062
TidsskriftNature Communications
Vol/bind14
Antal sider17
ISSN2041-1723
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
We are grateful to IMI-DIRECT study participants who volunteered for phenotyping, and clinical and technical staff across involved European study centres who contributed to recruitment and clinical assessment of study participants. The work leading to this publication has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement 115317 (DIRECT), resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution. Information on the initiatives and activities of the IMI-DIRECT research consortium is available at https://directdiabetes.org .

Publisher Copyright:
© 2023, Springer Nature Limited.

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