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Genome-wide screen of otosclerosis in population biobanks: 27 loci and shared associations with skeletal structure

Author

Listed:
  • Joel T. Rämö

    (University of Helsinki)

  • Tuomo Kiiskinen

    (University of Helsinki)

  • Richard Seist

    (Stanford University School of Medicine)

  • Kristi Krebs

    (University of Tartu)

  • Masahiro Kanai

    (University of Helsinki
    Broad Institute of Harvard and MIT
    Broad Institute of Harvard and MIT
    Massachusetts General Hospital)

  • Juha Karjalainen

    (University of Helsinki
    Broad Institute of Harvard and MIT
    Broad Institute of Harvard and MIT
    Massachusetts General Hospital)

  • Mitja Kurki

    (University of Helsinki
    Broad Institute of Harvard and MIT
    Broad Institute of Harvard and MIT
    Massachusetts General Hospital)

  • Eija Hämäläinen

    (University of Helsinki)

  • Paavo Häppölä

    (University of Helsinki)

  • Aki S. Havulinna

    (University of Helsinki
    Finnish Institute for Health and Welfare)

  • Heidi Hautakangas

    (University of Helsinki)

  • Reedik Mägi

    (University of Tartu)

  • Priit Palta

    (University of Helsinki
    University of Tartu)

  • Tõnu Esko

    (University of Tartu)

  • Andres Metspalu

    (University of Tartu)

  • Matti Pirinen

    (University of Helsinki
    University of Helsinki
    University of Helsinki)

  • Konrad J. Karczewski

    (University of Helsinki
    Broad Institute of Harvard and MIT
    Broad Institute of Harvard and MIT
    Massachusetts General Hospital)

  • Samuli Ripatti

    (University of Helsinki
    Broad Institute of Harvard and MIT
    Massachusetts General Hospital
    University of Helsinki)

  • Lili Milani

    (University of Tartu)

  • Konstantina M. Stankovic

    (Stanford University School of Medicine)

  • Antti Mäkitie

    (University of Helsinki and HUS Helsinki University Hospital)

  • Mark J. Daly

    (University of Helsinki
    Broad Institute of Harvard and MIT
    Broad Institute of Harvard and MIT
    Massachusetts General Hospital)

  • Aarno Palotie

    (University of Helsinki
    Broad Institute of Harvard and MIT
    Broad Institute of Harvard and MIT
    Massachusetts General Hospital)

Abstract

Otosclerosis is one of the most common causes of conductive hearing loss, affecting 0.3% of the population. It typically presents in adulthood and half of the patients have a positive family history. The pathophysiology of otosclerosis is poorly understood. A previous genome-wide association study (GWAS) identified a single association locus in an intronic region of RELN. Here, we report a meta-analysis of GWAS studies of otosclerosis in three population-based biobanks comprising 3504 cases and 861,198 controls. We identify 23 novel risk loci (p

Suggested Citation

  • Joel T. Rämö & Tuomo Kiiskinen & Richard Seist & Kristi Krebs & Masahiro Kanai & Juha Karjalainen & Mitja Kurki & Eija Hämäläinen & Paavo Häppölä & Aki S. Havulinna & Heidi Hautakangas & Reedik Mägi &, 2023. "Genome-wide screen of otosclerosis in population biobanks: 27 loci and shared associations with skeletal structure," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-022-32936-3
    DOI: 10.1038/s41467-022-32936-3
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    References listed on IDEAS

    as
    1. Konrad J. Karczewski & Laurent C. Francioli & Grace Tiao & Beryl B. Cummings & Jessica Alföldi & Qingbo Wang & Ryan L. Collins & Kristen M. Laricchia & Andrea Ganna & Daniel P. Birnbaum & Laura D. Gau, 2020. "The mutational constraint spectrum quantified from variation in 141,456 humans," Nature, Nature, vol. 581(7809), pages 434-443, May.
    2. Ida Surakka & Lars G. Fritsche & Wei Zhou & Joshua Backman & Jack A. Kosmicki & Haocheng Lu & Ben Brumpton & Jonas B. Nielsen & Maiken E. Gabrielsen & Anne Heidi Skogholt & Brooke Wolford & Sarah E. G, 2020. "MEPE loss-of-function variant associates with decreased bone mineral density and increased fracture risk," Nature Communications, Nature, vol. 11(1), pages 1-8, December.
    3. Christiaan A de Leeuw & Joris M Mooij & Tom Heskes & Danielle Posthuma, 2015. "MAGMA: Generalized Gene-Set Analysis of GWAS Data," PLOS Computational Biology, Public Library of Science, vol. 11(4), pages 1-19, April.
    4. Michael R. Bowl & Michelle M. Simon & Neil J. Ingham & Simon Greenaway & Luis Santos & Heather Cater & Sarah Taylor & Jeremy Mason & Natalja Kurbatova & Selina Pearson & Lynette R. Bower & Dave A. Cla, 2017. "A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    5. Clare Bycroft & Colin Freeman & Desislava Petkova & Gavin Band & Lloyd T. Elliott & Kevin Sharp & Allan Motyer & Damjan Vukcevic & Olivier Delaneau & Jared O’Connell & Adrian Cortes & Samantha Welsh &, 2018. "The UK Biobank resource with deep phenotyping and genomic data," Nature, Nature, vol. 562(7726), pages 203-209, October.
    6. Gao Wang & Abhishek Sarkar & Peter Carbonetto & Matthew Stephens, 2020. "A simple new approach to variable selection in regression, with application to genetic fine mapping," Journal of the Royal Statistical Society Series B, Royal Statistical Society, vol. 82(5), pages 1273-1300, December.
    7. Xiaomeng Wang & Robin E. Harris & Laura J. Bayston & Hilary L. Ashe, 2008. "Type IV collagens regulate BMP signalling in Drosophila," Nature, Nature, vol. 455(7209), pages 72-77, September.
    8. Mary E. Dickinson & Ann M. Flenniken & Xiao Ji & Lydia Teboul & Michael D. Wong & Jacqueline K. White & Terrence F. Meehan & Wolfgang J. Weninger & Henrik Westerberg & Hibret Adissu & Candice N. Baker, 2016. "High-throughput discovery of novel developmental phenotypes," Nature, Nature, vol. 537(7621), pages 508-514, September.
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