A large meta-analysis identifies genes associated with anterior uveitis
-
Published:2023-11-11
Issue:1
Volume:14
Page:
-
ISSN:2041-1723
-
Container-title:Nature Communications
-
language:en
-
Short-container-title:Nat Commun
Author:
Gelfman Sahar, Moscati Arden, Huergo Santiago Mendez, Wang Rujin, Rajagopal Veera, Parikshak NeelroopORCID, Pounraja Vijay KumarORCID, Chen Esteban, Leblanc Michelle, Hazlewood RalphORCID, Freudenberg Jan, Cooper Blerta, Ligocki Ann J., Miller Charles G., Van Zyl Tavé, Weyne Jonathan, Romano Carmelo, Sagdullaev Botir, Melander Olle, Baras ArisORCID, Zhang Aaron, Mansfield Adam J., Locke Adam, Pandey Aditeya, Campos Adrian, Ghosh Arkopravo, Gorovits Alexander, Lopez Alexander, Hawes Alicia, Fenney Alison, Averitt Amelia, Joshi Amit, Damask Amy, Bunyea Andrew, Ziyatdinov Andrey, Pandit Anita, Perez-Beals Ann, Alkelai Anna, Marcketta Anthony, Baldassari Antoine, Ayer Ariane, Gilly Arthur, Rasool Ayesha, Guvenek Aysegul, Geraghty Benjamin, Sultan Benjamin, Palmer William, Ye Bin, Zhang Blair, Boutkov Boris, Hobbs Brian, Forsythe Caitlin, Sidore Carlo, Paulding Charles, Wang Chenggu, Beechert Christina, Gillies Christopher, Zhang Chuanyi, Willer Cristen J., Li Dadong, Sharma Deepika, Stahl Eli, Austin Eliot, Jorgenson Eric, Brian Erin D., Mayerhofer Ernst, Edelstein Evan, Maxwell Evan K., Tzoneva Gannie, Hindy George, Mitra George, Solari Gina, Eom Gisu, Du Hang, Khiabanian Hossein, Kosmicki Jack, Otto Jacqueline, Hernandez Jaimee, Clauer Janice, Mighty Jason, Staples Jeffrey C., Rico-Varela Jennifer, Brown Jessie, He Jing, Zhang Jingning, Revez Joana, Hankins Jody, Mbatchou Joelle, Rivera-Picart Johannie, Silver John, Bovijn Jonas, Marchini Jonathan, Ross Jonathan, Bras Jose, Herman Joseph, Backman Joshua, Guan Ju, Rodriguez-Flores Juan, Mower Justin, Landheer Karl, Sun Kathie, Burch Kathy, Sosina Kayode, Manoochehri Kia, Skead Kimberly, Punuru Krishna Pawan, Guevara Kristy, Wu Kuan-Han, Watanabe Kyoko, Zhang Lance, Cremona Laura M., Gurski Lauren, Chen Lei, Ganel Liron, Sun Luanluan, Habegger Lukas, Pradhan Manasi, Kapoor Manav, Ferreira Manuel Allen Revez, Jones Marcus B., Padilla Maria Sotiropoulos, Suciu Maria Cristina, Ghoussaini Maya, Haas Mary, Lattari Michael, Kessler Michael, LeBlanc Michelle G., Pagan Michelle, Tang Mira, Riaz Moeen, Nafde Mona, Sarwar Mudasar, Rana Nadia, Lin Nan, Verweij Niek, Banerjee Nilanjana, Nishtala Nirupama, Krasheninina Olga, Delaneau Oliver, Sosina Olukayode, Akbari Parsa, Dornbos Peter, VandeHaar Peter, Challa Prathyusha, Nakka Priyanka, Schwartz Randi, Reynoso Raymond, Panea Razvan, Schiavo Ricardo, Guerreiro Rita, Lanche Rouel, Vedantam Sailaja, Martinez Salvador Romero, Choi Sam, Zarate Samantha, Malhotra Sameer, Hart Samuel, Sreeram Sanjay, Wolf Sarah E., Graham Sarah, Vrieze Scott, O’Keeffe Sean, Yu Sean, Gaynor Sheila, Alvarez Silvia, Balasubramanian Suganthi, Gokhale Sujit, Siceron Sunilbe, Bao Suying, De Tanima, Thornton Timothy, Polanco Tommy, Joseph Tyler, Zavala Valentina, Kumar Vijay, Mahajan Vrushali, Salerno William J., Bai Xiaodong, Zou Yuxin, Gu Zhenhua, Ferrando Adolfo, Shuldiner Alan, Deubler Andrew, Economides Aris, Abecasis Gonçalo Rocha, Reid Jeffrey G., Overton John D., Siminovitch Katherine, Lotta Luca A., Mitnaul Lyndon J., Cantor Michael, Stahl Eli A.ORCID, Coppola GiovanniORCID,
Abstract
AbstractAnterior 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.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference59 articles.
1. Durrani, O. M. et al. Degree, duration, and causes of visual loss in uveitis. Br. J. Ophthalmol. 88, 1159–1162 (2004). 2. Rosenbaum, J. T. et al. New observations and emerging ideas in diagnosis and management of non-infectious uveitis: A review. Semin Arthritis Rheum. 49, 438–445 (2019). 3. Thorne, J. E. et al. Prevalence of noninfectious uveitis in the United States: A claims-based analysis. JAMA Ophthalmol. 134, 1237–1245 (2016). 4. Joltikov, K. A. & Lobo-Chan, A. M. Epidemiology and risk factors in non-infectious uveitis: A systematic review. Front Med. (Lausanne) 8, 695904 (2021). 5. Chang, J. H. & Wakefield, D. Uveitis: a global perspective. Ocul. Immunol. Inflamm. 10, 263–279 (2002).
|
|