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Association of Risk Variants in the CFH Gene With Elevated Levels of Coagulation and Complement Factors in Idiopathic Multifocal Choroiditis
- Source :
- de Groot , E L , Ossewaarde-van Norel , J , de Boer , J H , Hiddingh , S , Bakker , B , van Huet , R A C , Ten Dam-van Loon , N H , Thiadens , A A H J , Meester-Smoor , M A , de Jong-Hesse , Y , Los , L I , den Hollander , A I , Boon , C J F , Kiemeney , L A , van Eijk , K R , Bakker , M K , Hoyng , C B & Kuiper , J J W 2023 , ' Association of Risk Variants in the CFH Gene With Elevated Levels of Coagulation and Complement Factors in Idiopathic Multifocal Choroiditis ' , JAMA Ophthalmology , vol. 141 , no. 8 , pp. 737-745 .
- Publication Year :
- 2023
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Abstract
- Importance: Idiopathic multifocal choroiditis (MFC) is poorly understood, thereby hindering optimal treatment and monitoring of patients. Objective: To identify the genes and pathways associated with idiopathic MFC. Design, Setting, and Participants: This was a case-control genome-wide association study (GWAS) and protein study of blood plasma samples conducted from March 2006 to February 2022. This was a multicenter study involving 6 Dutch universities. Participants were grouped into 2 cohorts: cohort 1 consisted of Dutch patients with idiopathic MFC and controls, and cohort 2 consisted of patients with MFC and controls. Plasma samples from patients with idiopathic MFC who had not received treatment were subjected to targeted proteomics. Idiopathic MFC was diagnosed according to the Standardization of Uveitis Nomenclature (SUN) Working Group guidelines for punctate inner choroidopathy and multifocal choroiditis with panuveitis. Data were analyzed from July 2021 to October 2022. Main outcomes and measures: Genetic variants associated with idiopathic MFC and risk variants associated with plasma protein concentrations in patients. Results: This study included a total of 4437 participants in cohort 1 (170 [3.8%] Dutch patients with idiopathic MFC and 4267 [96.2%] controls; mean [SD] age, 55 [18] years; 2443 female [55%]) and 1344 participants in cohort 2 (52 [3.9%] patients with MFC and 1292 [96.1%] controls; 737 male [55%]). The primary GWAS association mapped to the CFH gene with genome-wide significance (lead variant the A allele of rs7535263; odds ratio [OR], 0.52; 95% CI, 0.41-0.64; P = 9.3 × 10-9). There was no genome-wide significant association with classical human leukocyte antigen (HLA) alleles (lead classical allele, HLA-A*31:01; P = .002). The association with rs7535263 showed consistent direction of effect in an independent cohort of 52 cases and 1292 control samples (combined meta-analysis OR, 0.58; 95% CI, 0.38-0.77; P = 3.0 × 10-8). In proteomic anal
Details
- Database :
- OAIster
- Journal :
- de Groot , E L , Ossewaarde-van Norel , J , de Boer , J H , Hiddingh , S , Bakker , B , van Huet , R A C , Ten Dam-van Loon , N H , Thiadens , A A H J , Meester-Smoor , M A , de Jong-Hesse , Y , Los , L I , den Hollander , A I , Boon , C J F , Kiemeney , L A , van Eijk , K R , Bakker , M K , Hoyng , C B & Kuiper , J J W 2023 , ' Association of Risk Variants in the CFH Gene With Elevated Levels of Coagulation and Complement Factors in Idiopathic Multifocal Choroiditis ' , JAMA Ophthalmology , vol. 141 , no. 8 , pp. 737-745 .
- Notes :
- application/pdf, English
- Publication Type :
- Electronic Resource
- Accession number :
- edsoai.on1398451839
- Document Type :
- Electronic Resource