IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-022-32936-3.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-32936-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-32936-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. 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.
    2. 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.
    3. 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.
    4. 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.
    5. 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.
    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. 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.
    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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Benjamin B. Sun & Stephanie J. Loomis & Fabrizio Pizzagalli & Natalia Shatokhina & Jodie N. Painter & Christopher N. Foley & Megan E. Jensen & Donald G. McLaren & Sai Spandana Chintapalli & Alyssa H. , 2022. "Genetic map of regional sulcal morphology in the human brain from UK biobank data," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Qingbo S. Wang & Ryuya Edahiro & Ho Namkoong & Takanori Hasegawa & Yuya Shirai & Kyuto Sonehara & Hiromu Tanaka & Ho Lee & Ryunosuke Saiki & Takayoshi Hyugaji & Eigo Shimizu & Kotoe Katayama & Masahir, 2022. "The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    3. Eeva Sliz & Jaakko S. Tyrmi & Nilufer Rahmioglu & Krina T. Zondervan & Christian M. Becker & Outi Uimari & Johannes Kettunen, 2023. "Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. Mary P. LaPierre & Katherine Lawler & Svenja Godbersen & I. Sadaf Farooqi & Markus Stoffel, 2022. "MicroRNA-7 regulates melanocortin circuits involved in mammalian energy homeostasis," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    5. Vincent Michaud & Eulalie Lasseaux & David J. Green & Dave T. Gerrard & Claudio Plaisant & Tomas Fitzgerald & Ewan Birney & Benoît Arveiler & Graeme C. Black & Panagiotis I. Sergouniotis, 2022. "The contribution of common regulatory and protein-coding TYR variants to the genetic architecture of albinism," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    6. Sylvia Hartmann & Summaira Yasmeen & Benjamin M. Jacobs & Spiros Denaxas & Munir Pirmohamed & Eric R. Gamazon & Mark J. Caulfield & Harry Hemingway & Maik Pietzner & Claudia Langenberg, 2023. "ADRA2A and IRX1 are putative risk genes for Raynaud’s phenomenon," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    7. Nicole Deflaux & Margaret Sunitha Selvaraj & Henry Robert Condon & Kelsey Mayo & Sara Haidermota & Melissa A. Basford & Chris Lunt & Anthony A. Philippakis & Dan M. Roden & Joshua C. Denny & Anjene Mu, 2023. "Demonstrating paths for unlocking the value of cloud genomics through cross cohort analysis," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    8. Ruoyu Tian & Tian Ge & Hyeokmoon Kweon & Daniel B. Rocha & Max Lam & Jimmy Z. Liu & Kritika Singh & Daniel F. Levey & Joel Gelernter & Murray B. Stein & Ellen A. Tsai & Hailiang Huang & Christopher F., 2024. "Whole-exome sequencing in UK Biobank reveals rare genetic architecture for depression," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    9. Isabelle Austin-Zimmerman & Daniel F. Levey & Olga Giannakopoulou & Joseph D. Deak & Marco Galimberti & Keyrun Adhikari & Hang Zhou & Spiros Denaxas & Haritz Irizar & Karoline Kuchenbaecker & Andrew M, 2023. "Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    10. Magdalena Zimoń & Yunfeng Huang & Anthi Trasta & Aliaksandr Halavatyi & Jimmy Z. Liu & Chia-Yen Chen & Peter Blattmann & Bernd Klaus & Christopher D. Whelan & David Sexton & Sally John & Wolfgang Hube, 2021. "Pairwise effects between lipid GWAS genes modulate lipid plasma levels and cellular uptake," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    11. Sophie A. Riesmeijer & Zoha Kamali & Michael Ng & Dmitriy Drichel & Bram Piersma & Kerstin Becker & Thomas B. Layton & Jagdeep Nanchahal & Michael Nothnagel & Ahmad Vaez & Hans Christian Hennies & Pau, 2024. "A genome-wide association meta-analysis implicates Hedgehog and Notch signaling in Dupuytren’s disease," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    12. Zhiqiang Sha & Dick Schijven & Amaia Carrion-Castillo & Marc Joliot & Bernard Mazoyer & Simon E. Fisher & Fabrice Crivello & Clyde Francks, 2021. "The genetic architecture of structural left–right asymmetry of the human brain," Nature Human Behaviour, Nature, vol. 5(9), pages 1226-1239, September.
    13. Yunfeng Huang & Dora Bodnar & Chia-Yen Chen & Gabriela Sanchez-Andrade & Mark Sanderson & Jun Shi & Katherine G. Meilleur & Matthew E. Hurles & Sebastian S. Gerety & Ellen A. Tsai & Heiko Runz, 2023. "Rare genetic variants impact muscle strength," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
    14. H. Serhat Tetikol & Deniz Turgut & Kubra Narci & Gungor Budak & Ozem Kalay & Elif Arslan & Sinem Demirkaya-Budak & Alexey Dolgoborodov & Duygu Kabakci-Zorlu & Vladimir Semenyuk & Amit Jain & Brandi N., 2022. "Pan-African genome demonstrates how population-specific genome graphs improve high-throughput sequencing data analysis," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    15. Milton Pividori & Sumei Lu & Binglan Li & Chun Su & Matthew E. Johnson & Wei-Qi Wei & Qiping Feng & Bahram Namjou & Krzysztof Kiryluk & Iftikhar J. Kullo & Yuan Luo & Blair D. Sullivan & Benjamin F. V, 2023. "Projecting genetic associations through gene expression patterns highlights disease etiology and drug mechanisms," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    16. Jeffrey D. Wall & J. Fah Sathirapongsasuti & Ravi Gupta & Asif Rasheed & Radha Venkatesan & Saurabh Belsare & Ramesh Menon & Sameer Phalke & Anuradha Mittal & John Fang & Deepak Tanneeru & Manjari Des, 2023. "South Asian medical cohorts reveal strong founder effects and high rates of homozygosity," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    17. Charley Xia & Sarah J. Pickett & David C. M. Liewald & Alexander Weiss & Gavin Hudson & W. David Hill, 2023. "The contributions of mitochondrial and nuclear mitochondrial genetic variation to neuroticism," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    18. Suzanne Vogelezang & Jonathan P Bradfield & Tarunveer S Ahluwalia & John A Curtin & Timo A Lakka & Niels Grarup & Markus Scholz & Peter J van der Most & Claire Monnereau & Evie Stergiakouli & Anni Hei, 2020. "Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits," PLOS Genetics, Public Library of Science, vol. 16(10), pages 1-26, October.
    19. Andrew D. Grotzinger & Travis T. Mallard & Zhaowen Liu & Jakob Seidlitz & Tian Ge & Jordan W. Smoller, 2023. "Multivariate genomic architecture of cortical thickness and surface area at multiple levels of analysis," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    20. Tzu-Ting Chen & Jaeyoung Kim & Max Lam & Yi-Fang Chuang & Yen-Ling Chiu & Shu-Chin Lin & Sang-Hyuk Jung & Beomsu Kim & Soyeon Kim & Chamlee Cho & Injeong Shim & Sanghyeon Park & Yeeun Ahn & Aysu Okbay, 2024. "Shared genetic architectures of educational attainment in East Asian and European populations," Nature Human Behaviour, Nature, vol. 8(3), pages 562-575, March.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-022-32936-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.