Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations | September 2021 | Cell

Cindy G.Boer147KonstantinosHatzikotoulas247LorraineSoutham247LiljaStefánsdóttir3YanfeiZhang4RodrigoCoutinho de Almeida5Tian T.Wu6JieZheng7AprilHartley78MarisTeder-Laving9Anne HeidiSkogholt10ChikashiTerao11EleniZengini12GeorgeAlexiadis13AndreiBarysenka2GydaBjornsdottir3Maiken E.Gabrielsen10ArthurGilly2EleftheriaZeggini24648

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.

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