| Title: | Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations |
| Journal: | Cell |
| Published: | 26 Aug 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/34450027/ |
| DOI: | https://doi.org/10.1016/j.cell.2021.07.038 |
| URL: | http://www.cell.com/article/S0092867421009417/pdf |
Publication 10223
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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.</p>
159 Authors
- Cindy G. Boer
- Konstantinos Hatzikotoulas
- Lorraine Southam
- Lilja Stefánsdóttir
- Yanfei Zhang
- Rodrigo Coutinho de Almeida
- Tian T. Wu
- Jie Zheng
- April Hartley
- Maris Teder-Laving
- Anne Heidi Skogholt
- Chikashi Terao
- Eleni Zengini
- George Alexiadis
- Andrei Barysenka
- Gyda Bjornsdottir
- Maiken E. Gabrielsen
- Arthur Gilly
- Thorvaldur Ingvarsson
- Marianne B. Johnsen
- Helgi Jonsson
- Margreet Kloppenburg
- Almut Luetge
- Sigrun H. Lund
- Reedik Mägi
- Massimo Mangino
- Rob R.G.H.H. Nelissen
- Manu Shivakumar
- Julia Steinberg
- Hiroshi Takuwa
- Laurent F. Thomas
- Margo Tuerlings
- arcOGEN Consortium
- 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
- HUNT All-In Pain
- Amy E. Martinsen
- Cristen Willer
- Egil Andreas Fors
- Ingunn Mundal
- Knut Hagen
- Kristian Bernhard Nilsen
- Marie Udnesseter Lie
- Sigrid Børte
- Ben Brumpton
- Jonas Bille Nielsen
- Lars G. Fritsche
- Wei Zhou
- Ingrid Heuch
- Kjersti Storheim
- ARGO Consortium
- Evangelos Tyrpenou
- Athanasios Koukakis
- Dimitrios Chytas
- Dimitrios Stergios Evangelopoulos
- Chronopoulos Efstathios
- Spiros Pneumaticos
- Vasileios S. Nikolaou
- Konstantinos Malizos
- Lydia Anastasopoulou
- Regeneron Genetics Center
- Goncalo Abecasis
- Aris Baras
- Michael Cantor
- Giovanni Coppola
- Andrew Deubler
- Aris Economides
- Luca A. Lotta
- John D. Overton
- Jeffrey G. Reid
- Alan Shuldiner
- Katia Karalis
- Katherine Siminovitch
- Christina Beechert
- Caitlin Forsythe
- Erin D. Fuller
- Zhenhua Gu
- Michael Lattari
- Alexander Lopez
- Thomas D. Schleicher
- Maria Sotiropoulos Padilla
- Louis Widom
- Sarah E. Wolf
- Manasi Pradhan
- Kia Manoochehri
- Xiaodong Bai
- Suganthi Balasubramanian
- Boris Boutkov
- Gisu Eom
- Lukas Habegger
- Alicia Hawes
- Olga Krasheninina
- Rouel Lanche
- Adam J. Mansfield
- Evan K. Maxwell
- Mona Nafde
- Sean O'Keeffe
- Max Orelus
- Razvan Panea
- Tommy Polanco
- Ayesha Rasool
- William Salerno
- Jeffrey C. Staples
- Dadong Li
- Deepika Sharma
- Ilanjana Banerjee
- Jonas Bovijn
- Adam Locke
- Niek Verweij
- Mary Haas
- George Hindy
- Tanima De
- Parsa Akbari
- Olukayode Sosina
- Manuel A.R. Ferreira
- Marcus B. Jones
- Jason Mighty
- Michelle G. LeBlanc
- Lyndon J. Mitnaul
- George C. Babis
- Jason Pui Yin Cheung
- Jae Hee Kang
- Peter Kraft
- Steven A. Lietman
- Dino Samartzis
- P. Eline Slagboom
- Kari Stefansson
- Unnur Thorsteinsdottir
- Jonathan H. Tobias
- André G. Uitterlinden
- Bendik Winsvold
- John-Anker Zwart
- George Davey Smith
- Pak Chung Sham
- Gudmar Thorleifsson
- Tom R. Gaunt
- Andrew P. Morris
- Ana M. Valdes
- Aspasia Tsezou
- Kathryn S.E. Cheah
- Shiro Ikegawa
- Kristian Hveem
- Tõnu Esko
- J. Mark Wilkinson
- Ingrid Meulenbelt
- Ming Ta Michael Lee
- Joyce B.J. van Meurs
- Unnur Styrkársdóttir
- Eleftheria Zeggini
Enabling scientific discoveries that improve human health