A large meta-analysis identifies genes associated with anterior uveitis

作者：Sahar Gelfman, Arden Moscati, Santiago Méndez Huergo, Rujin Wang, Veera M. Rajagopal, Neelroop Parikshak, Vijay Kumar Pounraja, Esteban Chen, Michelle G. LeBlanc, Ralph J. Hazlewood, Jan Freudenberg, Blerta Cooper, Ann J. Ligocki, Charles G. Miller, Tavé van Zyl, Jonathan Weyne, Carmelo Romano, Botir T. Sagdullaev, Olle Melander, Aris Baras, Aaron Zhang, Adam J. Mansfield, Adam E. Locke, Aditeya Pandey, Adrián I. Campos, Arkopravo Ghosh, Alexander Gorovits, Alexander Lopez, Alicia Hawes, Alison Fenney, Amelia Averitt, Amit D. Joshi, Amy Damask, Andrew Bunyea, Andrey Ziyatdinov, Anita Pandit, Ann Perez-Beals, Anna Alkelai, Anthony Marcketta, Antoine Baldassari, Ariane Ayer, Arthur Gilly, Ayesha Rasool, Ayşegül Güvenek, Benjamin Geraghty, Benjamin Sultan, William Palmer, Bin Ye, Blair Zhang, Boris Boutkov, Brian D. Hobbs, Caitlin Forsythe, Carlo Sidore, Charles Paulding, Chenggu Wang, Christina Beechert, Christopher E. Gillies, Chuanyi Zhang, Cristen J. Willer, Dadong Li, Deepika Sharma, Eli A. Stahl, Eliot Austin, Eric Jorgenson, Erin D. Brian, Ernst Mayerhofer, Evan Edelstein, Evan K. Maxwell, Gannie Tzoneva, George Hindy, George Mitra, Gina Solari, Gisu Eom, Hang Du, Hossein Khiabanian, Jack A. Kosmicki, Jacqueline M. Otto, Jaimee Hernandez, Janice Clauer, Jason Mighty, Jeffrey Staples, Jennifer Rico‐Varela, Jessie Brown, Jing He, Jingning Zhang, Joana Revez, Jody Hankins, Joelle Mbatchou, Johannie Rivera-Picart, John Silver, Jonas Bovijn, Jonathan Marchini, Jonathan Ross, José Brás, Joseph Herman, Joshua Backman, Ju Guan, Juan L. Rodríguez-Flores, Justin Mower, Karl Landheer, Kathie Sun, Kathy Burch, Kayode Sosina, Kia Manoochehri, Kimberly Skead, Krishna Pawan Punuru, Kristy Guevara, Kuan-Han H. Wu, Kyoko Watanabe, Lance Zhang, Laura M. Cremona, Lauren Gurski, Lei Chen, Liron Ganel, Luanluan Sun, Lukas Habegger, Manasi Pradhan, Manav Kapoor, Manuel Allen Revez Ferreira, Marcus B. Jones, Maria Sotiropoulos Padilla, Maria Suciu, Maya Ghoussaini, Mary E. Haas, Michael Lattari, Michael D. Kessler, Michelle G. LeBlanc, Michelle Pagan, Mira Tang, Moeen Riaz, Mona Nafde, Mudasar Sarwar, Nadia Rana, Nan Lin, Niek Verweij, Nilanjana Banerjee, Nirupama Nishtala, Olga Krasheninina, Olivier Delaneau, Olukayode Sosina, Parsa Akbari, Peter Dornbos, Peter VandeHaar, Prathyusha Challa, Priyanka Nakka, Randi Schwartz, Raymond Reynoso, Razvan Panea, Ricardo Schiavo, Rita Guerreiro, Rouel Lanche, Sailaja Vedantam, Salvador Romero Martinez, Sam Choi, Samantha Zarate, Sameer Malhotra, Samuel F. M. Hart, Sanjay Sreeram, Sarah E. Wolf, Sarah E. Graham, Scott Vrieze, Sean O’Keeffe, Sean Yu, Sheila M. Gaynor, Silvia Álvarez, Suganthi Balasubramanian, Sujit Gokhale, Sunilbe Siceron, Suying Bao, Tanima De, Timothy A. Thornton, Tommy Polanco, Tyler Joseph, Valentina A. Zavala, Vijay Kumar, Vrushali Mahajan, William Salerno, Xiaodong Bai, Yuxin Zou, Zhenhua Gu, Adolfo A. Ferrando, Alan R. Shuldiner, Andrew Deubler, Aris N. Economides, Gonçalo Rocha Abecasis, Jeffrey G. Reid, John D. Overton, Katherine Siminovitch, Luca A. Lotta, Lyndon J. Mitnaul, Michael Cantor, Eli A. Stahl, Giovanni Coppola · 发表于：Nature Communications · 年份：2023 · DOI：10.1038/s41467-023-43036-1 · 被引用次数：22 · 研究领域：Ocular Diseases and Behçet’s Syndrome、Systemic Lupus Erythematosus Research、Otitis Media and Relapsing Polychondritis

Anterior Uveitis (AU) is the inflammation of the anterior part of the eye, the iris and ciliary body and is strongly associated with HLA-B*27. We report AU exome sequencing results from eight independent cohorts consisting of 3,850 cases and 916,549 controls. We identify common genome-wide significant loci in HLA-B (OR = 3.37, p = 1.03e-196) and ERAP1 (OR = 0.86, p = 1.1e-08), and find IPMK (OR = 9.4, p = 4.42e-09) and IDO2 (OR = 3.61, p = 6.16e-08) as genome-wide significant genes based on the burden of rare coding variants. Dividing the cohort into HLA-B*27 positive and negative individuals, we find ERAP1 haplotype is strongly protective only for B*27-positive AU (OR = 0.73, p = 5.2e-10). Investigation of B*27-negative AU identifies a common signal near HLA-DPB1 (rs3117230, OR = 1.26, p = 2.7e-08), risk genes IPMK and IDO2, and several additional candidate risk genes, including ADGFR5, STXBP2, and ACHE. Taken together, we decipher the genetics underlying B*27-positive and -negative AU and identify rare and common genetic signals for both subtypes of disease.