德国环境健康研究中心Eleftheria Zeggini小组的最新研究，通过对9个种群826,690个体进行分析揭示了骨关节炎遗传学。该研究于2021年8月26日发表于国际学术期刊《细胞》杂志。

研究人员对826,690个体（其中包涵骨关节炎患者177,517 名）进行了全基因组关联研究荟萃分析，确定了与11种不同表型骨关节炎有关的100种独立相关风险变异，其中有52种之前未报道与该疾病相关。该报告揭示了拇指和脊柱骨关节炎的风险变异，并确定承重和非承重关节之间的遗传效应差异。研究人员还确定了性别特异性和与早期发病年龄相关的骨关节炎风险位点。

研究整合了来自患者原发组织（包括关节软骨、软骨下骨和骨赘软骨）的功能基因组数据，并确定了高可信度的效应基因。研究人员提供与疼痛（主要疾病症状）相关表型的遗传相关性证据，并确定了与神经元之间的可能因果基因。该结果有利于理解骨关节炎发病过程中的关键分子，并可能促进潜在成药靶点的转化。

据悉，全球约有超过3亿人受骨关节炎的影响。

附：英文原文

Title: Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations

Author: 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 Mgi, Massimo Mangino, Rob R.G.H.H. 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, Egil Andreas Fors, Ingunn Mundal, Knut Hagen, Kristian Bernhard Nilsen, Marie Udnesseter Lie, Sigrid Brte, Ben Brumpton, Jonas Bille Nielsen, Lars G. Fritsche, Wei Zhou, Ingrid Heuch, Kjersti Storheim, Evangelos Tyrpenou, Athanasios Koukakis, Dimitrios Chytas, Dimitrios Stergios Evangelopoulos, Chronopoulos Efstathios, Spiros Pneumaticos, Vasileios S. Nikolaou, Konstantinos Malizos, Lydia Anastasopoulou, 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

Issue&Volume: 2021-08-26

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.

DOI: 10.1016/j.cell.2021.07.038

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00941-7