A large meta-analysis identifies genes associated with anterior uveitis

Sahar Gelfman; Arden Moscati; Santiago Mendez Huergo; Rujin Wang; Veera Rajagopal; Neelroop Parikshak; Vijay Kumar Pounraja; Esteban Chen; Michelle Leblanc; Ralph Hazlewood; Jan Freudenberg; Blerta Cooper; Ann J. Ligocki; Charles G. Miller; Tavé Van Zyl; Jonathan Weyne; Carmelo Romano; Botir Sagdullaev; Olle Melander; Aris Baras; Aaron Zhang; Adam J. Mansfield; Adam Locke; Aditeya Pandey; Adrian Campos; Arkopravo Ghosh; Alexander Gorovits; Alexander Lopez; Alicia Hawes; Alison Fenney; Amelia Averitt; Amit Joshi; Amy Damask; Andrew Bunyea; Andrey Ziyatdinov; Anita Pandit; Ann Perez-Beals; Anna Alkelai; Anthony Marcketta; Antoine Baldassari; Ariane Ayer; Arthur Gilly; Ayesha Rasool; Aysegul Guvenek; Benjamin Geraghty; Benjamin Sultan; William Palmer; Bin Ye; Blair Zhang; Boris Boutkov; Brian Hobbs; Caitlin Forsythe; Carlo Sidore; Charles Paulding; Chenggu Wang; Christina Beechert; Christopher Gillies; Chuanyi Zhang; Cristen J. Willer; Dadong Li; Deepika Sharma; Eli 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 Kosmicki; Jacqueline Otto; Jaimee Hernandez; Janice Clauer; Jason Mighty; Jeffrey C. 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; Jose Bras; Joseph Herman; Joshua Backman; Ju Guan; Juan Rodriguez-Flores; Justin Mower; Karl Landheer; Kathie Sun; Kathy Burch; Kayode Sosina; Kia Manoochehri; Kimberly Skead; Krishna Pawan Punuru; Kristy Guevara; Kuan Han 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 Cristina Suciu; Maya Ghoussaini; Mary Haas; Michael Lattari; Michael 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; Oliver 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 Hart; Sanjay Sreeram; Sarah E. Wolf; Sarah Graham; Scott Vrieze; Sean O’Keeffe; Sean Yu; Sheila Gaynor; Silvia Alvarez; Suganthi Balasubramanian; Sujit Gokhale; Sunilbe Siceron; Suying Bao; Tanima De; Timothy Thornton; Tommy Polanco; Tyler Joseph; Valentina Zavala; Vijay Kumar; Vrushali Mahajan; William J. Salerno; Xiaodong Bai; Yuxin Zou; Zhenhua Gu; Adolfo Ferrando; Alan Shuldiner; Andrew Deubler; Aris 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

doi:10.1038/s41467-023-43036-1

A large meta-analysis identifies genes associated with anterior uveitis

Sahar Gelfman, Arden Moscati, Santiago Mendez Huergo, Rujin Wang, Veera Rajagopal, Neelroop Parikshak, Vijay Kumar Pounraja, Esteban Chen, Michelle Leblanc, Ralph Hazlewood, Jan Freudenberg, Blerta Cooper, Ann J. Ligocki, Charles G. Miller, Tavé Van Zyl, Jonathan Weyne, Carmelo Romano, Botir Sagdullaev, Olle Melander, Aris BarasAaron Zhang, Adam J. Mansfield, Adam Locke, Aditeya Pandey, Adrian Campos, Arkopravo Ghosh, Alexander Gorovits, Alexander Lopez, Alicia Hawes, Alison Fenney, Amelia Averitt, Amit Joshi, Amy Damask, Andrew Bunyea, Andrey Ziyatdinov, Anita Pandit, Ann Perez-Beals, Anna Alkelai, Anthony Marcketta, Antoine Baldassari, Ariane Ayer, Arthur Gilly, Ayesha Rasool, Aysegul Guvenek, Benjamin Geraghty, Benjamin Sultan, William Palmer, Bin Ye, Blair Zhang, Boris Boutkov, Brian Hobbs, Caitlin Forsythe, Carlo Sidore, Charles Paulding, Chenggu Wang, Christina Beechert, Christopher Gillies, Chuanyi Zhang, Cristen J. Willer, Dadong Li, Deepika Sharma, Eli 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 Kosmicki, Jacqueline Otto, Jaimee Hernandez, Janice Clauer, Jason Mighty, Jeffrey C. 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, Jose Bras, Joseph Herman, Joshua Backman, Ju Guan, Juan Rodriguez-Flores, Justin Mower, Karl Landheer, Kathie Sun, Kathy Burch, Kayode Sosina, Kia Manoochehri, Kimberly Skead, Krishna Pawan Punuru, Kristy Guevara, Kuan Han 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 Cristina Suciu, Maya Ghoussaini, Mary Haas, Michael Lattari, Michael 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, Oliver 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 Hart, Sanjay Sreeram, Sarah E. Wolf, Sarah Graham, Scott Vrieze, Sean O’Keeffe, Sean Yu, Sheila Gaynor, Silvia Alvarez, Suganthi Balasubramanian, Sujit Gokhale, Sunilbe Siceron, Suying Bao, Tanima De, Timothy Thornton, Tommy Polanco, Tyler Joseph, Valentina Zavala, Vijay Kumar, Vrushali Mahajan, William J. Salerno, Xiaodong Bai, Yuxin Zou, Zhenhua Gu, Adolfo Ferrando, Alan Shuldiner, Andrew Deubler, Aris 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

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English (US)
Article number	7300
Journal	Nature communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-43036-1
State	Published - Dec 2023
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2023, The Author(s).

PubMed: MeSH publication types

Meta-Analysis
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

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10.1038/s41467-023-43036-1

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Gelfman, S., Moscati, A., Huergo, S. M., Wang, R., Rajagopal, V., Parikshak, N., Pounraja, V. K., Chen, E., Leblanc, M., Hazlewood, R., Freudenberg, J., Cooper, B., Ligocki, A. J., Miller, C. G., Van Zyl, T., Weyne, J., Romano, C., Sagdullaev, B., Melander, O., ... Coppola, G. (2023). A large meta-analysis identifies genes associated with anterior uveitis. Nature communications, 14(1), Article 7300. https://doi.org/10.1038/s41467-023-43036-1

Gelfman, S, Moscati, A, Huergo, SM, Wang, R, Rajagopal, V, Parikshak, N, Pounraja, VK, Chen, E, Leblanc, M, Hazlewood, R, Freudenberg, J, Cooper, B, Ligocki, AJ, Miller, CG, Van Zyl, T, Weyne, J, Romano, C, Sagdullaev, B, Melander, O, Baras, A, Zhang, A, Mansfield, AJ, Locke, A, Pandey, A, Campos, A, Ghosh, A, Gorovits, A, Lopez, A, Hawes, A, Fenney, A, Averitt, A, Joshi, A, Damask, A, Bunyea, A, Ziyatdinov, A, Pandit, A, Perez-Beals, A, Alkelai, A, Marcketta, A, Baldassari, A, Ayer, A, Gilly, A, Rasool, A, Guvenek, A, Geraghty, B, Sultan, B, Palmer, W, Ye, B, Zhang, B, Boutkov, B, Hobbs, B, Forsythe, C, Sidore, C, Paulding, C, Wang, C, Beechert, C, Gillies, C, Zhang, C, Willer, CJ, Li, D, Sharma, D, Stahl, E, Austin, E, Jorgenson, E, Brian, ED, Mayerhofer, E, Edelstein, E, Maxwell, EK, Tzoneva, G, Hindy, G, Mitra, G, Solari, G, Eom, G, Du, H, Khiabanian, H, Kosmicki, J, Otto, J, Hernandez, J, Clauer, J, Mighty, J, Staples, JC, Rico-Varela, J, Brown, J, He, J, Zhang, J, Revez, J, Hankins, J, Mbatchou, J, Rivera-Picart, J, Silver, J, Bovijn, J, Marchini, J, Ross, J, Bras, J, Herman, J, Backman, J, Guan, J, Rodriguez-Flores, J, Mower, J, Landheer, K, Sun, K, Burch, K, Sosina, K, Manoochehri, K, Skead, K, Punuru, KP, Guevara, K, Wu, KH, Watanabe, K, Zhang, L, Cremona, LM, Gurski, L, Chen, L, Ganel, L, Sun, L, Habegger, L, Pradhan, M, Kapoor, M, Ferreira, MAR, Jones, MB, Padilla, MS, Suciu, MC, Ghoussaini, M, Haas, M, Lattari, M, Kessler, M, LeBlanc, MG, Pagan, M, Tang, M, Riaz, M, Nafde, M, Sarwar, M, Rana, N, Lin, N, Verweij, N, Banerjee, N, Nishtala, N, Krasheninina, O, Delaneau, O, Sosina, O, Akbari, P, Dornbos, P, VandeHaar, P, Challa, P, Nakka, P, Schwartz, R, Reynoso, R, Panea, R, Schiavo, R, Guerreiro, R, Lanche, R, Vedantam, S, Martinez, SR, Choi, S, Zarate, S, Malhotra, S, Hart, S, Sreeram, S, Wolf, SE, Graham, S, Vrieze, S, O’Keeffe, S, Yu, S, Gaynor, S, Alvarez, S, Balasubramanian, S, Gokhale, S, Siceron, S, Bao, S, De, T, Thornton, T, Polanco, T, Joseph, T, Zavala, V, Kumar, V, Mahajan, V, Salerno, WJ, Bai, X, Zou, Y, Gu, Z, Ferrando, A, Shuldiner, A, Deubler, A, Economides, A, Abecasis, GR, Reid, JG, Overton, JD, Siminovitch, K, Lotta, LA, Mitnaul, LJ, Cantor, M, Stahl, EA & Coppola, G 2023, 'A large meta-analysis identifies genes associated with anterior uveitis', Nature communications, vol. 14, no. 1, 7300. https://doi.org/10.1038/s41467-023-43036-1

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title = "A large meta-analysis identifies genes associated with anterior uveitis",

abstract = "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.",

author = "Sahar Gelfman and Arden Moscati and Huergo, {Santiago Mendez} and Rujin Wang and Veera Rajagopal and Neelroop Parikshak and Pounraja, {Vijay Kumar} and Esteban Chen and Michelle Leblanc and Ralph Hazlewood and Jan Freudenberg and Blerta Cooper and Ligocki, {Ann J.} and Miller, {Charles G.} and {Van Zyl}, Tav{\'e} and Jonathan Weyne and Carmelo Romano and Botir Sagdullaev and Olle Melander and Aris Baras and Aaron Zhang and Mansfield, {Adam J.} and Adam Locke and Aditeya Pandey and Adrian Campos and Arkopravo Ghosh and Alexander Gorovits and Alexander Lopez and Alicia Hawes and Alison Fenney and Amelia Averitt and Amit Joshi and Amy Damask and Andrew Bunyea and Andrey Ziyatdinov and Anita Pandit and Ann Perez-Beals and Anna Alkelai and Anthony Marcketta and Antoine Baldassari and Ariane Ayer and Arthur Gilly and Ayesha Rasool and Aysegul Guvenek and Benjamin Geraghty and Benjamin Sultan and William Palmer and Bin Ye and Blair Zhang and Boris Boutkov and Brian Hobbs and Caitlin Forsythe and Carlo Sidore and Charles Paulding and Chenggu Wang and Christina Beechert and Christopher Gillies and Chuanyi Zhang and Willer, {Cristen J.} and Dadong Li and Deepika Sharma and Eli Stahl and Eliot Austin and Eric Jorgenson and Brian, {Erin D.} and Ernst Mayerhofer and Evan Edelstein and Maxwell, {Evan K.} and Gannie Tzoneva and George Hindy and George Mitra and Gina Solari and Gisu Eom and Hang Du and Hossein Khiabanian and Jack Kosmicki and Jacqueline Otto and Jaimee Hernandez and Janice Clauer and Jason Mighty and Staples, {Jeffrey C.} and Jennifer Rico-Varela and Jessie Brown and Jing He and Jingning Zhang and Joana Revez and Jody Hankins and Joelle Mbatchou and Johannie Rivera-Picart and John Silver and Jonas Bovijn and Jonathan Marchini and Jonathan Ross and Jose Bras and Joseph Herman and Joshua Backman and Ju Guan and Juan Rodriguez-Flores and Justin Mower and Karl Landheer and Kathie Sun and Kathy Burch and Kayode Sosina and Kia Manoochehri and Kimberly Skead and Punuru, {Krishna Pawan} and Kristy Guevara and Wu, {Kuan Han} and Kyoko Watanabe and Lance Zhang and Cremona, {Laura M.} and Lauren Gurski and Lei Chen and Liron Ganel and Luanluan Sun and Lukas Habegger and Manasi Pradhan and Manav Kapoor and Ferreira, {Manuel Allen Revez} and Jones, {Marcus B.} and Padilla, {Maria Sotiropoulos} and Suciu, {Maria Cristina} and Maya Ghoussaini and Mary Haas and Michael Lattari and Michael Kessler and LeBlanc, {Michelle G.} and Michelle Pagan and Mira Tang and Moeen Riaz and Mona Nafde and Mudasar Sarwar and Nadia Rana and Nan Lin and Niek Verweij and Nilanjana Banerjee and Nirupama Nishtala and Olga Krasheninina and Oliver Delaneau and Olukayode Sosina and Parsa Akbari and Peter Dornbos and Peter VandeHaar and Prathyusha Challa and Priyanka Nakka and Randi Schwartz and Raymond Reynoso and Razvan Panea and Ricardo Schiavo and Rita Guerreiro and Rouel Lanche and Sailaja Vedantam and Martinez, {Salvador Romero} and Sam Choi and Samantha Zarate and Sameer Malhotra and Samuel Hart and Sanjay Sreeram and Wolf, {Sarah E.} and Sarah Graham and Scott Vrieze and Sean O{\textquoteright}Keeffe and Sean Yu and Sheila Gaynor and Silvia Alvarez and Suganthi Balasubramanian and Sujit Gokhale and Sunilbe Siceron and Suying Bao and Tanima De and Timothy Thornton and Tommy Polanco and Tyler Joseph and Valentina Zavala and Vijay Kumar and Vrushali Mahajan and Salerno, {William J.} and Xiaodong Bai and Yuxin Zou and Zhenhua Gu and Adolfo Ferrando and Alan Shuldiner and Andrew Deubler and Aris Economides and Abecasis, {Gon{\c c}alo Rocha} and Reid, {Jeffrey G.} and Overton, {John D.} and Katherine Siminovitch and Lotta, {Luca A.} and Mitnaul, {Lyndon J.} and Michael Cantor and Stahl, {Eli A.} and Giovanni Coppola",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = dec,

doi = "10.1038/s41467-023-43036-1",

language = "English (US)",

volume = "14",

journal = "Nature communications",

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TY - JOUR

T1 - A large meta-analysis identifies genes associated with anterior uveitis

AU - Gelfman, Sahar

AU - Moscati, Arden

AU - Huergo, Santiago Mendez

AU - Wang, Rujin

AU - Rajagopal, Veera

AU - Parikshak, Neelroop

AU - Pounraja, Vijay Kumar

AU - Chen, Esteban

AU - Leblanc, Michelle

AU - Hazlewood, Ralph

AU - Freudenberg, Jan

AU - Cooper, Blerta

AU - Ligocki, Ann J.

AU - Miller, Charles G.

AU - Van Zyl, Tavé

AU - Weyne, Jonathan

AU - Romano, Carmelo

AU - Sagdullaev, Botir

AU - Melander, Olle

AU - Baras, Aris

AU - Zhang, Aaron

AU - Mansfield, Adam J.

AU - Locke, Adam

AU - Pandey, Aditeya

AU - Campos, Adrian

AU - Ghosh, Arkopravo

AU - Gorovits, Alexander

AU - Lopez, Alexander

AU - Hawes, Alicia

AU - Fenney, Alison

AU - Averitt, Amelia

AU - Joshi, Amit

AU - Damask, Amy

AU - Bunyea, Andrew

AU - Ziyatdinov, Andrey

AU - Pandit, Anita

AU - Perez-Beals, Ann

AU - Alkelai, Anna

AU - Marcketta, Anthony

AU - Baldassari, Antoine

AU - Ayer, Ariane

AU - Gilly, Arthur

AU - Rasool, Ayesha

AU - Guvenek, Aysegul

AU - Geraghty, Benjamin

AU - Sultan, Benjamin

AU - Palmer, William

AU - Ye, Bin

AU - Zhang, Blair

AU - Boutkov, Boris

AU - Hobbs, Brian

AU - Forsythe, Caitlin

AU - Sidore, Carlo

AU - Paulding, Charles

AU - Wang, Chenggu

AU - Beechert, Christina

AU - Gillies, Christopher

AU - Zhang, Chuanyi

AU - Willer, Cristen J.

AU - Li, Dadong

AU - Sharma, Deepika

AU - Stahl, Eli

AU - Austin, Eliot

AU - Jorgenson, Eric

AU - Brian, Erin D.

AU - Mayerhofer, Ernst

AU - Edelstein, Evan

AU - Maxwell, Evan K.

AU - Tzoneva, Gannie

AU - Hindy, George

AU - Mitra, George

AU - Solari, Gina

AU - Eom, Gisu

AU - Du, Hang

AU - Khiabanian, Hossein

AU - Kosmicki, Jack

AU - Otto, Jacqueline

AU - Hernandez, Jaimee

AU - Clauer, Janice

AU - Mighty, Jason

AU - Staples, Jeffrey C.

AU - Rico-Varela, Jennifer

AU - Brown, Jessie

AU - He, Jing

AU - Zhang, Jingning

AU - Revez, Joana

AU - Hankins, Jody

AU - Mbatchou, Joelle

AU - Rivera-Picart, Johannie

AU - Silver, John

AU - Bovijn, Jonas

AU - Marchini, Jonathan

AU - Ross, Jonathan

AU - Bras, Jose

AU - Herman, Joseph

AU - Backman, Joshua

AU - Guan, Ju

AU - Rodriguez-Flores, Juan

AU - Mower, Justin

AU - Landheer, Karl

AU - Sun, Kathie

AU - Burch, Kathy

AU - Sosina, Kayode

AU - Manoochehri, Kia

AU - Skead, Kimberly

AU - Punuru, Krishna Pawan

AU - Guevara, Kristy

AU - Wu, Kuan Han

AU - Watanabe, Kyoko

AU - Zhang, Lance

AU - Cremona, Laura M.

AU - Gurski, Lauren

AU - Chen, Lei

AU - Ganel, Liron

AU - Sun, Luanluan

AU - Habegger, Lukas

AU - Pradhan, Manasi

AU - Kapoor, Manav

AU - Ferreira, Manuel Allen Revez

AU - Jones, Marcus B.

AU - Padilla, Maria Sotiropoulos

AU - Suciu, Maria Cristina

AU - Ghoussaini, Maya

AU - Haas, Mary

AU - Lattari, Michael

AU - Kessler, Michael

AU - LeBlanc, Michelle G.

AU - Pagan, Michelle

AU - Tang, Mira

AU - Riaz, Moeen

AU - Nafde, Mona

AU - Sarwar, Mudasar

AU - Rana, Nadia

AU - Lin, Nan

AU - Verweij, Niek

AU - Banerjee, Nilanjana

AU - Nishtala, Nirupama

AU - Krasheninina, Olga

AU - Delaneau, Oliver

AU - Sosina, Olukayode

AU - Akbari, Parsa

AU - Dornbos, Peter

AU - VandeHaar, Peter

AU - Challa, Prathyusha

AU - Nakka, Priyanka

AU - Schwartz, Randi

AU - Reynoso, Raymond

AU - Panea, Razvan

AU - Schiavo, Ricardo

AU - Guerreiro, Rita

AU - Lanche, Rouel

AU - Vedantam, Sailaja

AU - Martinez, Salvador Romero

AU - Choi, Sam

AU - Zarate, Samantha

AU - Malhotra, Sameer

AU - Hart, Samuel

AU - Sreeram, Sanjay

AU - Wolf, Sarah E.

AU - Graham, Sarah

AU - Vrieze, Scott

AU - O’Keeffe, Sean

AU - Yu, Sean

AU - Gaynor, Sheila

AU - Alvarez, Silvia

AU - Balasubramanian, Suganthi

AU - Gokhale, Sujit

AU - Siceron, Sunilbe

AU - Bao, Suying

AU - De, Tanima

AU - Thornton, Timothy

AU - Polanco, Tommy

AU - Joseph, Tyler

AU - Zavala, Valentina

AU - Kumar, Vijay

AU - Mahajan, Vrushali

AU - Salerno, William J.

AU - Bai, Xiaodong

AU - Zou, Yuxin

AU - Gu, Zhenhua

AU - Ferrando, Adolfo

AU - Shuldiner, Alan

AU - Deubler, Andrew

AU - Economides, Aris

AU - Abecasis, Gonçalo Rocha

AU - Reid, Jeffrey G.

AU - Overton, John D.

AU - Siminovitch, Katherine

AU - Lotta, Luca A.

AU - Mitnaul, Lyndon J.

AU - Cantor, Michael

AU - Stahl, Eli A.

AU - Coppola, Giovanni

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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.

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U2 - 10.1038/s41467-023-43036-1

DO - 10.1038/s41467-023-43036-1

M3 - Article

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AN - SCOPUS:85176222319

SN - 2041-1723

VL - 14

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 7300

ER -

A large meta-analysis identifies genes associated with anterior uveitis

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