Title :

Representation of Women Among Individuals With Mild Variants in ABCA4-Associated Retinopathy: A Meta-Analysis

Author(s) :

Cornelis, Stéphanie S. [Auteur]
Department of Human Genetics [Nijmegen]
Inthout, Joanna [Auteur]
Radboud University Medical Center [Nijmegen]
Runhart, Esmee H. [Auteur]
Grunewald, Olivier [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Lin, Siying [Auteur]
Moorfields Eye Hospital
University College of London [London] [UCL]
Corradi, Zelia [Auteur]
Department of Human Genetics [Nijmegen]
Khan, Mubeen [Auteur]
Max Planck Institute for Psycholinguistics
Department of Human Genetics [Nijmegen]
Hitti-Malin, Rebekkah J. [Auteur]
Department of Human Genetics [Nijmegen]
Whelan, Laura [Auteur]
Trinity College Dublin
Farrar, G. Jane [Auteur]
Trinity College Dublin
Sharon, Dror [Auteur]
Hadassah Hebrew University Medical Center [Jerusalem]
Van Den Born, L. Ingeborgh [Auteur]
Arno, Gavin [Auteur]
Moorfields Eye Hospital
University College of London [London] [UCL]
Simcoe, Mark [Auteur]
Moorfields Eye Hospital
University College of London [London] [UCL]
Michaelides, Michel [Auteur]
Moorfields Eye Hospital
University College of London [London] [UCL]
Webster, Andrew R. [Auteur]
Moorfields Eye Hospital
University College of London [London] [UCL]
Roosing, Susanne [Auteur]
Department of Human Genetics [Nijmegen]
Mahroo, Omar A. [Auteur]
Moorfields Eye Hospital
University College of London [London] [UCL]
Dhaenens, Claire-Marie [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Cremers, Frans P. M. [Auteur]
Department of Human Genetics [Nijmegen]

Journal title :

JAMA Ophthalmology

Abbreviated title :

JAMA Ophthalmol

Volume number :

142

Pages :

463-471

Publisher :

American Medical Association

Publication date :

2024-04-11

ISSN :

2168-6173

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Importance Previous studies indicated that female sex might be a modifier in Stargardt disease, which is an ABCA4-associated retinopathy. Objective To investigate whether women are overrepresented among individuals ...
Show more >Importance Previous studies indicated that female sex might be a modifier in Stargardt disease, which is an ABCA4-associated retinopathy. Objective To investigate whether women are overrepresented among individuals with ABCA4-associated retinopathy who are carrying at least 1 mild allele or carrying nonmild alleles. Data Sources Literature data, data from 2 European centers, and a new study. Data from a Radboudumc database and from the Rotterdam Eye Hospital were used for exploratory hypothesis testing. Study Selection Studies investigating the sex ratio in individuals with ABCA4-AR and data from centers that collected ABCA4 variant and sex data. The literature search was performed on February 1, 2023; data from the centers were from before 2023. Data Extraction and Synthesis Random-effects meta-analyses were conducted to test whether the proportions of women among individuals with ABCA4-associated retinopathy with mild and nonmild variants differed from 0.5, including subgroup analyses for mild alleles. Sensitivity analyses were performed excluding data with possibly incomplete variant identification. χ2 Tests were conducted to compare the proportions of women in adult-onset autosomal non–ABCA4-associated retinopathy and adult-onset ABCA4-associated retinopathy and to investigate if women with suspected ABCA4-associated retinopathy are more likely to obtain a genetic diagnosis. Data analyses were performed from March to October 2023. Main Outcomes and Measures Proportion of women per ABCA4-associated retinopathy group. The exploratory testing included sex ratio comparisons for individuals with ABCA4-associated retinopathy vs those with other autosomal retinopathies and for individuals with ABCA4-associated retinopathy who underwent genetic testing vs those who did not. Results Women were significantly overrepresented in the mild variant group (proportion, 0.59; 95% CI, 0.56-0.62; P < .001) but not in the nonmild variant group (proportion, 0.50; 95% CI, 0.46-0.54; P = .89). Sensitivity analyses confirmed these results. Subgroup analyses on mild variants showed differences in the proportions of women. Furthermore, in the Radboudumc database, the proportion of adult women among individuals with ABCA4-associated retinopathy (652/1154 = 0.56) was 0.10 (95% CI, 0.05-0.15) higher than among individuals with other retinopathies (280/602 = 0.47). Conclusions and Relevance This meta-analysis supports the likelihood that sex is a modifier in developing ABCA4-associated retinopathy for individuals with a mild ABCA4 allele. This finding may be relevant for prognosis predictions and recurrence risks for individuals with ABCA4-associated retinopathy. Future studies should further investigate whether the overrepresentation of women is caused by differences in the disease mechanism, by differences in health care–seeking behavior, or by health care discrimination between women and men with ABCA4-AR.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Research team(s) :

Alzheimer et Tauopathies

Submission date :

2024-05-06T22:31:09Z
2025-03-07T15:18:18Z