A genome-wide meta-analysis uncovers six sequence variants conferring risk of vertigo

Skuladottir, Astros Th; Bjornsdottir, Gyda; Nawaz, Muhammad Sulaman; Petersen, Hannes; Rognvaldsson, Solvi; Moore, Kristjan Helgi Swerford; Olafsson, Pall I.; Magnusson, Sigurður H.; Bjornsdottir, Anna; Sveinsson, Olafur A.; Sigurdardottir, Gudrun R.; Sævarsdóttir, Sædís; Ivarsdottir, Erna V.; Stefánsdóttir, Lilja; Gunnarsson, Bjarni; Muhlestein, Joseph B.; Knowlton, Kirk U.; Jones, David A.; Nadauld, Lincoln D.; Hartmann, Annette M.; Rujescu, Dan; Strupp, Michael; Walters, Guðmundur Bragi; Thorgeirsson, Thorgeir E.; Jónsdóttir, Ingileif; Holm, Hilma; Thorleifsson, Gudmar; Gudbjartsson, Daniel F.; Sulem, Patrick; Stefansson, Hreinn; Stefansson, Kari

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A genome-wide meta-analysis uncovers six sequence variants conferring risk of vertigo

Titill:	A genome-wide meta-analysis uncovers six sequence variants conferring risk of vertigo
Höfundur:	Skuladottir, Astros Th Bjornsdottir, Gyda orcid.org/0000-0002-8100-0306 Nawaz, Muhammad Sulaman Petersen, Hannes orcid.org/0000-0002-2327-523X Rognvaldsson, Solvi Moore, Kristjan Helgi Swerford Olafsson, Pall I. Magnusson, Sigurður H. Bjornsdottir, Anna Sveinsson, Olafur A. ... 21 fleiri höfundar Sýna alla höfunda Sigurdardottir, Gudrun R. Sævarsdóttir, Sædís Ivarsdottir, Erna V. Stefánsdóttir, Lilja Gunnarsson, Bjarni Muhlestein, Joseph B. Knowlton, Kirk U. Jones, David A. Nadauld, Lincoln D. Hartmann, Annette M. Rujescu, Dan Strupp, Michael Walters, Guðmundur Bragi Thorgeirsson, Thorgeir E. Jónsdóttir, Ingileif Holm, Hilma orcid.org/0000-0002-9517-6636 Thorleifsson, Gudmar orcid.org/0000-0003-4623-9087 Gudbjartsson, Daniel F. Sulem, Patrick orcid.org/0000-0001-7123-6123 Stefansson, Hreinn orcid.org/0000-0002-9331-6666 Stefansson, Kari orcid.org/0000-0003-1676-864X 31 höfundar Sýna færri höfunda
Útgáfa:	2021-10-07
Tungumál:	Enska
Umfang:	1622211
Háskóli/Stofnun:	Landspitali - The National University Hospital of Iceland
Deild:	Faculty of Medicine Other departments
Birtist í:	Communications Biology; 4(1)
ISSN:	2399-3642
DOI:	10.1038/s42003-021-02673-2
Efnisorð:	Svimi; Eyru; Genamengi; Erfðafræði; Ear, Inner/growth & development; Genome, Human; Genome-Wide Association Study; Humans; Labyrinth Diseases/genetics; Mutation, Missense; Vertigo/genetics; General Agricultural and Biological Sciences; General Biochemistry,Genetics and Molecular Biology; Medicine (miscellaneous)
URI:	https://hdl.handle.net/20.500.11815/3217
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Tilvitnun: Skuladottir , A T , Bjornsdottir , G , Nawaz , M S , Petersen , H , Rognvaldsson , S , Moore , K H S , Olafsson , P I , Magnusson , S H , Bjornsdottir , A , Sveinsson , O A , Sigurdardottir , G R , Sævarsdóttir , S , Ivarsdottir , E V , Stefánsdóttir , L , Gunnarsson , B , Muhlestein , J B , Knowlton , K U , Jones , D A , Nadauld , L D , Hartmann , A M , Rujescu , D , Strupp , M , Walters , G B , Thorgeirsson , T E , Jónsdóttir , I , Holm , H , Thorleifsson , G , Gudbjartsson , D F , Sulem , P , Stefansson , H & Stefansson , K 2021 , ' A genome-wide meta-analysis uncovers six sequence variants conferring risk of vertigo ' , Communications Biology , vol. 4 , no. 1 , 1148 , pp. 1148 . https://doi.org/10.1038/s42003-021-02673-2
Útdráttur: Vertigo is the leading symptom of vestibular disorders and a major risk factor for falls. In a genome-wide association study of vertigo (Ncases = 48,072, Ncontrols = 894,541), we uncovered an association with six common sequence variants in individuals of European ancestry, including missense variants in ZNF91, OTOG, OTOGL, and TECTA, and a cis-eQTL for ARMC9. The association of variants in ZNF91, OTOGL, and OTOP1 was driven by an association with benign paroxysmal positional vertigo. Using previous reports of sequence variants associating with age-related hearing impairment and motion sickness, we found eight additional variants that associate with vertigo. Although disorders of the auditory and the vestibular system may co-occur, none of the six genome-wide significant vertigo variants were associated with hearing loss and only one was associated with age-related hearing impairment. Our results uncovered sequence variants associating with vertigo in a genome-wide association study and implicated genes with known roles in inner ear development, maintenance, and disease.
Athugasemdir: Funding Information: We thank the participants in this study for their valuable contribution to research. We also thank our colleagues at deCODE who contributed to genotyping and analysis of the WGS data. This research was conducted using the UK Biobank Resource (application number 24898). We acknowledge Stacey Knight, Tyler Barker, Jeffrey L. Anderson, and John F. Carlquist for their contribution to the HerediGene: Population study. We acknowledge the participants and investigators of the FinnGen study. The financial support from the European Commission to the NeuroPain project (FP7#HEALTH-2013-602891-2) and painFACT project (H2020-2020-848099), and the National Institutes of Health (R01DE022905) is acknowledged. Publisher Copyright: © 2021, The Author(s).