PMID- 32492107 OWN - NLM STAT- MEDLINE DCOM- 20210101 LR - 20210110 IS - 1552-5783 (Electronic) IS - 0146-0404 (Print) IS - 0146-0404 (Linking) VI - 61 IP - 6 DP - 2020 Jun 3 TI - Genomewide Association Study of Acute Anterior Uveitis Identifies New Susceptibility Loci. PG - 3 LID - 10.1167/iovs.61.6.3 [doi] LID - 3 AB - PURPOSE: Acute anterior uveitis (AAU) is a common intraocular inflammatory disease. AAU occurs in 30% to 50% of patients with ankylosing spondylitis (AS), and both conditions are strongly associated with human leukocyte antigen (HLA)-B27, implying a shared etiology. This study aims to apply genomewide association study (GWAS) to characterize the genetic associations of AAU and their relationship to the genetics of AS. METHODS: We undertook the GWAS analyses in 2752 patients with AS with AAU (cases) and 3836 patients with AS without AAU (controls). There were 7,436,415 single-nucleotide polymorphisms (SNPs) available after SNP microarray genotyping, imputation, and quality-control filtering. RESULTS: We identified one locus associated with AAU at genomewide significance: rs9378248 (P = 2.69 x 10-8, odds ratio [OR] = 0.78), lying close to HLA-B. Suggestive association was observed at 11 additional loci, including previously reported AS loci ERAP1 (rs27529, P = 2.19 x 10-7, OR = 1.22) and NOS2 (rs2274894, P = 8.22 x 10-7, OR = 0.83). Multiple novel suggestive associations were also identified, including MERTK (rs10171979, P = 2.56 x 10-6, OR = 1.20), KIFAP3 (rs508063, P = 5.64 x 10-7, OR = 1.20), CLCN7 (rs67412457, P = 1.33 x 10-6, OR = 1.25), ACAA2 (rs9947182, P = 9.70 x 10-7, OR = 1.37), and 5 intergenic loci. The SNP-based heritability is approximately 0.5 for AS alone, and is much higher (approximately 0.7) for AS with AAU. Consistent with the high heritability, a genomewide polygenic risk score shows strong power in identifying individuals at high risk of either AS with AAU or AS alone. CONCLUSIONS: We report here the first GWAS for AAU and identify new susceptibility loci. Our findings confirm the strong overlap in etiopathogenesis of AAU with AS, and also provide new insights into the genetic basis of AAU. FAU - Huang, Xiu-Feng AU - Huang XF AD - ,. AD - ,. AD - ,. FAU - Li, Zhixiu AU - Li Z AD - ,. FAU - De Guzman, Erika AU - De Guzman E AD - ,. FAU - Robinson, Philip AU - Robinson P AD - Brisbane Hospital,. FAU - Gensler, Lianne AU - Gensler L AD - ,. FAU - Ward, Michael M AU - Ward MM AD - ,. FAU - Rahbar, Mohammad Hossein AU - Rahbar MH AD - ,. FAU - Lee, MinJae AU - Lee M AD - ,. FAU - Weisman, Michael H AU - Weisman MH AD - ,. FAU - Macfarlane, Gary J AU - Macfarlane GJ AD - ,. AD - ,. FAU - Jones, Gareth T AU - Jones GT AD - ,. AD - ,. FAU - Klingberg, Eva AU - Klingberg E AD - ,. AD - ,. FAU - Forsblad-d'Elia, Helena AU - Forsblad-d'Elia H AD - ,. AD - ,. FAU - McCluskey, Peter AU - McCluskey P AD - ,. FAU - Wakefield, Denis AU - Wakefield D AD - ,. FAU - Coombes, Jeff S AU - Coombes JS AD - ,. FAU - Fiatarone Singh, Maria A AU - Fiatarone Singh MA AD - ,. FAU - Mavros, Yorgi AU - Mavros Y AD - ,. FAU - Vlahovich, Nicole AU - Vlahovich N AD - ,. FAU - Hughes, David C AU - Hughes DC AD - ,. FAU - Marzo-Ortega, Helena AU - Marzo-Ortega H AD - ,. AD - ,. FAU - Van der Horste-Bruinsma, Irene AU - Van der Horste-Bruinsma I AD - ,. FAU - O'Shea, Finbar AU - O'Shea F AD - , St. James's Hospital,. FAU - Martin, Tammy M AU - Martin TM AD - ,. FAU - Rosenbaum, James AU - Rosenbaum J AD - ,. FAU - Breban, Maxime AU - Breban M AD - ,. AD - ,. AD - , Universite Paris Diderot,. FAU - Jin, Zi-Bing AU - Jin ZB AD - ,. AD - ,. FAU - Leo, Paul AU - Leo P AD - ,. FAU - Reveille, John D AU - Reveille JD AD - ,. FAU - Wordsworth, B Paul AU - Wordsworth BP AD - ,. FAU - Brown, Matthew A AU - Brown MA AD - ,. AD - ,. LA - eng GR - DH_/Department of Health/United Kingdom GR - 076113/WT_/Wellcome Trust/United Kingdom GR - R01 AR046208/AR/NIAMS NIH HHS/United States GR - 19536/ARC_/Arthritis Research UK/United Kingdom GR - M01 RR000425/RR/NCRR NIH HHS/United States GR - WT_/Wellcome Trust/United Kingdom GR - 18797/ARC_/Arthritis Research UK/United Kingdom PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, N.I.H., Intramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Invest Ophthalmol Vis Sci JT - Investigative ophthalmology & visual science JID - 7703701 RN - 0 (HLA-B Antigens) SB - IM MH - Acute Disease MH - Adult MH - Case-Control Studies MH - Female MH - Genetic Loci/*genetics MH - Genetic Predisposition to Disease/*genetics MH - *Genome-Wide Association Study MH - Genotyping Techniques MH - HLA-B Antigens/genetics MH - Humans MH - Male MH - Middle Aged MH - Odds Ratio MH - *Polymorphism, Single Nucleotide MH - Spondylitis, Ankylosing/genetics MH - Uveitis, Anterior/*genetics PMC - PMC7415282 COIS- Disclosure: X.-F. Huang, None; Z. Li, None; E. De Guzman, None; P. Robinson, None; L. Gensler, None; M.M. Ward, None; M.H. Rahbar, None; M. Lee, None; M.H. Weisman, None; G.J. Macfarlane, None; G.T. Jones, None; E. Klingberg, None; H. Forsblad-d'Elia, None; P. McCluskey, None; D. Wakefield, None; J.S. Coombes, None; M.A. Fiatarone Singh, None; Y. Mavros, None; N. Vlahovich, None; D.C. Hughes, None; H. Marzo-Ortega, None; I. Van der Horste-Bruinsma, None; F. O'Shea, None; T.M. Martin, None; J. Rosenbaum, None; M. Breban, None; Z.-B. Jin, None; P. Leo, None; J.D. Reveille, None; B.P. Wordsworth, None; M.A. Brown, None EDAT- 2020/06/04 06:00 MHDA- 2021/01/02 06:00 PMCR- 2020/06/03 CRDT- 2020/06/04 06:00 PHST- 2020/06/04 06:00 [entrez] PHST- 2020/06/04 06:00 [pubmed] PHST- 2021/01/02 06:00 [medline] PHST- 2020/06/03 00:00 [pmc-release] AID - 2766288 [pii] AID - IOVS-19-28859 [pii] AID - 10.1167/iovs.61.6.3 [doi] PST - ppublish SO - Invest Ophthalmol Vis Sci. 2020 Jun 3;61(6):3. doi: 10.1167/iovs.61.6.3.