作者
Cindy G. Boer,Konstantinos Hatzikotoulas,Lorraine Southam,Lilja Stefánsdóttir,Yanfei Zhang,Rodrigo Coutinho de Almeida,Tian Wu,Jie Zheng,April Hartley,Maris Teder‐Laving,Anne Heidi Skogholt,Chikashi Terao,Eleni Zengini,G Alexiadis,Andrei Barysenka,Gyða Björnsdóttir,Maiken E. Gabrielsen,Arthur Gilly,Þorvaldur Ingvarsson,Marianne Bakke Johnsen,Helgi Jónsson,Margreet Kloppenburg,Almut Luetge,Sigrún H. Lund,Reedik Mägi,Massimo Mangino,Rob R.G.H.H. Nelissen,Manu Shivakumar,Julia Steinberg,Hiroshi Takuwa,Laurent F. Thomas,Margo Tuerlings,Hunt All-In Pain,George C. Babis,Jason Pui Yin Cheung,Jae H. Kang,Peter Kraft,Steven A. Lietman,Dino Samartzis,P. Eline Slagboom,Kāri Stefánsson,Unnur Þorsteinsdóttir,Jonathan H Tobias,André G. Uitterlinden,Bendik S. Winsvold,John‐Anker Zwart,George Davey Smith,Pak C. Sham,Guðmar Þorleifsson,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
摘要
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.