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Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations

Authors :
arcOGEN Consortium
HUNT All-In Pain
ARGO Consortium
Regeneron Genetics Center
C.G. (Cindy) Boer
Konstantinos Hatzikotoulas
Lorraine Southam
Lilja Stefánsdóttir
Yanfei Zhang
R. Coutinho de Almeida
Tian T. Wu
Jie Zheng
AE (April) Hartley
Maris Teder-Laving
Anne Heidi Skogholt
Chikashi Terao
Eleni Zengini
George Alexiadis
Andrei Barysenka
Gyda Bjornsdottir
Maiken Elvestad Gabrielsen
Arthur Gilly
Thorvaldur Ingvarsson
Marianne B. Johnsen
Helgi Jonsson
Margreet Kloppenburg
Almut Luetge
Sigrun H. Lund
Reedik Mägi
Massimo Mangino
RGHH (Rob) Nelissen
Manu Shivakumar
Julia Steinberg
Hiroshi Takuwa
Laurent F. Thomas
Margo Tuerlings
John Loughlin
Nigel Arden
Fraser Birrell
Andrew Carr
Panos Deloukas
Michael Doherty
Andrew W. McCaskie
William E.R. Ollier
Ashok Rai
Stuart H. Ralston
Tim D. Spector
Gillian A. Wallis
Amy E. Martinsen
Cristen Willer
N (Niek) Verweij
PJA (Peter) van Kraft
A.G. (André) Uitterlinden
J.B.J. (Joyce) van Meurs
arcOGEN Consortium
HUNT All-In Pain
ARGO Consortium
Regeneron Genetics Center
C.G. (Cindy) Boer
Konstantinos Hatzikotoulas
Lorraine Southam
Lilja Stefánsdóttir
Yanfei Zhang
R. Coutinho de Almeida
Tian T. Wu
Jie Zheng
AE (April) Hartley
Maris Teder-Laving
Anne Heidi Skogholt
Chikashi Terao
Eleni Zengini
George Alexiadis
Andrei Barysenka
Gyda Bjornsdottir
Maiken Elvestad Gabrielsen
Arthur Gilly
Thorvaldur Ingvarsson
Marianne B. Johnsen
Helgi Jonsson
Margreet Kloppenburg
Almut Luetge
Sigrun H. Lund
Reedik Mägi
Massimo Mangino
RGHH (Rob) Nelissen
Manu Shivakumar
Julia Steinberg
Hiroshi Takuwa
Laurent F. Thomas
Margo Tuerlings
John Loughlin
Nigel Arden
Fraser Birrell
Andrew Carr
Panos Deloukas
Michael Doherty
Andrew W. McCaskie
William E.R. Ollier
Ashok Rai
Stuart H. Ralston
Tim D. Spector
Gillian A. Wallis
Amy E. Martinsen
Cristen Willer
N (Niek) Verweij
PJA (Peter) van Kraft
A.G. (André) Uitterlinden
J.B.J. (Joyce) van Meurs
Publication Year :
2021

Abstract

Osteoarthritis affects over 300 million people worldwide. Here, we conduct a genome-wide association study meta-analysis across 826,690 individuals (177,517 with osteoarthritis) and identify 100 independently associated risk variants across 11 osteoarthritis phenotypes, 52 of which have not been associated with the disease before. We report thumb and spine osteoarthritis risk variants and identify differences in genetic effects between weight-bearing and non-weight-bearing joints. We identify sex-specific and early age-at-onset osteoarthritis risk loci. We integrate functional genomics data from primary patient tissues (including articular cartilage, subchondral bone, and osteophytic cartilage) and identify high-confidence effector genes. We provide evidence for genetic correlation with phenotypes related to pain, the main disease symptom, and identify likely causal genes linked to neuronal processes. Our results provide insights into key molecular players in disease processes and highlight attractive drug targets to accelerate translation.

Details

Database :
OAIster
Notes :
Cell vol. 184 no. 18, pp. 4784-4818.e17
Publication Type :
Electronic Resource
Accession number :
edsoai.on1273464412
Document Type :
Electronic Resource
Full Text :
https://doi.org/10.1016.j.cell.2021.07.038