| Literature DB >> 34450027 |
Cindy G Boer1, Konstantinos Hatzikotoulas2, Lorraine Southam2, Lilja Stefánsdóttir3, Yanfei Zhang4, Rodrigo Coutinho de Almeida5, Tian T Wu6, Jie Zheng7, April Hartley8, Maris Teder-Laving9, Anne Heidi Skogholt10, Chikashi Terao11, Eleni Zengini12, George Alexiadis13, Andrei Barysenka2, Gyda Bjornsdottir3, Maiken E Gabrielsen10, Arthur Gilly2, Thorvaldur Ingvarsson14, Marianne B Johnsen15, Helgi Jonsson16, Margreet Kloppenburg17, Almut Luetge10, Sigrun H Lund3, Reedik Mägi9, Massimo Mangino18, Rob R G H H Nelissen19, Manu Shivakumar20, Julia Steinberg21, Hiroshi Takuwa22, Laurent F Thomas23, Margo Tuerlings5, George C Babis24, Jason Pui Yin Cheung25, Jae Hee Kang26, Peter Kraft27, Steven A Lietman28, Dino Samartzis29, P Eline Slagboom5, Kari Stefansson30, Unnur Thorsteinsdottir30, Jonathan H Tobias31, André G Uitterlinden1, Bendik Winsvold32, John-Anker Zwart33, George Davey Smith34, Pak Chung Sham35, Gudmar Thorleifsson3, Tom R Gaunt7, Andrew P Morris36, Ana M Valdes37, Aspasia Tsezou38, Kathryn S E Cheah39, Shiro Ikegawa40, Kristian Hveem41, Tõnu Esko9, J Mark Wilkinson42, Ingrid Meulenbelt5, Ming Ta Michael Lee43, Joyce B J van Meurs1, Unnur Styrkársdóttir3, Eleftheria Zeggini44.
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.Entities:
Keywords: drug targets; effector genes; functional genomics; genetic architecture; genome-wide association meta-analysis; osteoarthritis
Mesh：
Year: 2021 PMID： 34450027 PMCID： PMC8459317 DOI： 10.1016/j.cell.2021.07.038
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582