June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Ethnicity of pathogenic variants in the ABCA4 gene: analysis of allele frequency in the general population
Author Affiliations & Notes
  • Yu Fujinami-Yokokawa
    Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, National Hospital Organization, Tokyo Medical Center, Meguro-ku, TOKYO, Japan
    Graduate School of Health Management, Keio University, Tokyo, Japan, Shinjyuku-Ku, Tokyo, Japan
  • Izumi Naka
    Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
  • Nikolas Pontikos
    UCL Institute of Ophthalmology, University College London, London, London, United Kingdom
    Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, National Hospital Organization, Tokyo Medical Center, Meguro-ku, TOKYO, Japan
  • Gavin Arno
    UCL Institute of Ophthalmology, University College London, London, London, United Kingdom
    Moorfields Eye Hospital, London, London, United Kingdom
  • Lizhu Yang
    Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, National Hospital Organization, Tokyo Medical Center, Meguro-ku, TOKYO, Japan
    Department of Ophthalmology, Keio University, Shinjyuku-Ku, Tokyo, Japan
  • XIAO LIU
    Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, National Hospital Organization, Tokyo Medical Center, Meguro-ku, TOKYO, Japan
    Department of Ophthalmology, Keio University, Shinjyuku-Ku, Tokyo, Japan
  • Shiying Li
    Southwest Hospital/Southwest Eye Hospital, Chongqing, China
  • Se Joon Woo
    Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seoul, Korea (the Republic of)
  • Rene Moya
    Hospital Del Salvador, Universidad de Chile, Santiago, Chile
  • Kazushige Tsunoda
    Division of Vision Research, National Institute of Sensory Organs, National Hospital Organization, Tokyo Medical Center, Meguro-Ku, Tokyo, Japan
  • Hiroaki Miyata
    Graduate School of Health Management, Keio University, Tokyo, Japan, Shinjyuku-Ku, Tokyo, Japan
    Department of Health Policy and Management, School of Medicine, Keio University, Shinjyuku-Ku, Tokyo, Japan
  • Jun Ohashi
    Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
  • Rupert W. Strauss
    Department of Ophthalmology, Johannes Kepler University Linz, Linz, Austria
    Department of Ophthalmology, Medical University of Graz, Graz, Austria
  • Hendrik P Scholl
    Department of Ophthalmology, University of Basel, Basel, Switzerland
    Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland
  • Michel Michaelides
    UCL Institute of Ophthalmology, University College London, London, London, United Kingdom
    Moorfields Eye Hospital, London, London, United Kingdom
  • Kaoru Fujinami
    Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, National Hospital Organization, Tokyo Medical Center, Meguro-ku, TOKYO, Japan
    UCL Institute of Ophthalmology, University College London, London, London, United Kingdom
  • Footnotes
    Commercial Relationships   Yu Fujinami-Yokokawa, None; Izumi Naka, None; Nikolas Pontikos, Phenopolis Limited (E); Gavin Arno, None; Lizhu Yang, None; XIAO LIU, None; Shiying Li, None; Se Joon Woo, None; Rene Moya, None; Kazushige Tsunoda, None; Hiroaki Miyata, None; Jun Ohashi, None; Rupert Strauss, None; Hendrik Scholl, Astellas Institute for Regenerative Medicine (S), Foundation Fighting Blindness Clinical Research Institute (F), Gensight Biologics (S), Gerson Lehrman Group (C), Guidepoint (C), Gyroscope Therapeutics Ltd. (S), Ionis Pharmaceuticals, Inc. (S), Kinarus AG (F), Novartis Pharma AG (F), Novo Nordisk (S), Pharma Research & Early Development (pRED) of F. Hoffmann-La Roche Ltd (F), ReNeuron Group Plc/Ora Inc. (S), Wellcome Trust ("Pinnacle Study") (F), wiss National Science Foundation (National Center of Competence in Research Molecular Systems Engineering “Molecular Systems Engineering”) (F); Michel Michaelides, None; Kaoru Fujinami, Acucela Inc (C), Acucela Inc (R), Astellas Pharma Inc (C), Astellas Pharma Inc (R), Astellas Pharma Inc (F), Foundation Fighting Blindness (R), Janssen Pharmaceutical K.K. (S), Japanese Ophthalmology Society (R), Japan Retinitis Pigmentosa Society (R), Kubota Pharmaceutical Holdings Co., Ltd (C), Kubota Pharmaceutical Holdings Co., Ltd (R), MeiraGTx Ltd (S), NightstaRx Limited (R), Novartis Pharma K.K. (C), oundation Fighting Blindness Clinical Research Institute (R), Sanofi Genzyme (S), SANTEN Company (P)
  • Footnotes
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Investigative Ophthalmology & Visual Science June 2020, Vol.61, 2390. doi:
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      Yu Fujinami-Yokokawa, Izumi Naka, Nikolas Pontikos, Gavin Arno, Lizhu Yang, XIAO LIU, Shiying Li, Se Joon Woo, Rene Moya, Kazushige Tsunoda, Hiroaki Miyata, Jun Ohashi, Rupert W. Strauss, Hendrik P Scholl, Michel Michaelides, Kaoru Fujinami; Ethnicity of pathogenic variants in the ABCA4 gene: analysis of allele frequency in the general population. Invest. Ophthalmol. Vis. Sci. 2020;61(7):2390.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To investigate the ethnicity of the prevalent variants in the ABCA4 gene utilizing the allele frequency in the general population.

Methods : 1193 ABCA4 variants detected in 4794 subjects on the Leiden Open Variation Database (LOVD version 3.0; https://www.lovd.nl/) were reviewed. 567 recurrent variants reported more than twice were selected for analysis. Assessment of pathogenicity was performed for each variant according to the previously published method (Fujinami et el. ProgStar report 8. 2019), and 226 pathogenic/likely pathogenic/disease-associated variants with available allele frequency were investigated. The allele frequency in six ethnic groups (African, Latino, Jewish, East Asian, European, South Asian) was surveyed on the Genome Aggregation Database (gnomAD; https://gnomad.broadinstitute.org/). Prevalent variants for each ethnic group were selected (allele frequency>0.02%, allele count>2), and enrichment in one ethnic group compared to another group was statistically examined (Fisher’s exact test). All prevalent variants were classified into two groups; Group 1 - variants statistically enriched (p<0.05) for an ethnic group, and Group 2 - variants shared among multiple ethnic groups.

Results : Sixty-four prevalent pathogenic ABCA4 variants were identified to be enriched in African (n=15), Latino (n=11), Jewish (n=7), East Asian (n=13), European (n=15), and South Asian (n=3) groups. 43 variants were included in Group 1; African (11/15, 73.3%), Latino (8/11, 72.7%), Jewish (6/7, 85.7%), East Asian (7/13, 53.8%), European (8/15, 53.3%), and South Asian (3/3, 100.0%). Twenty-one variants were in Group 2; African (4/15, 26.7%), Latino (3/11, 27.3%), Jewish (1/7, 14.3%), East Asian (6/13, 46.2%), European (7/15, 46.7%), and South Asian (0/3, 0.0%).

Conclusions : Around two thirds of prevalent pathogenic ABCA4 variants were specific for an ethnic group. The proportion of ethnicity specific variants was highest in South Asian and lowest in European groups; although the inherent selection bias in the process of identification of ABCA4 variants on the public database should be considered. These results help in the interpretation of detected variants, ethnicity-based genotype-phenotype correlation studies, as well as ethnicity-based counselling of patients.

This is a 2020 ARVO Annual Meeting abstract.

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