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

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

Title: A genome-wide meta-analysis uncovers six sequence variants conferring risk of vertigo
Author: 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 more authors Show all authors
Date: 2021-10-07
Language: English
Scope: 1622211
University/Institute: Landspitali - The National University Hospital of Iceland
Department: Faculty of Medicine
Other departments
Series: Communications Biology; 4(1)
ISSN: 2399-3642
DOI: 10.1038/s42003-021-02673-2
Subject: 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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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


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.


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).

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