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

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

*Corresponding author for this work

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Abstract

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.

Original languageEnglish
Article number1148
Pages (from-to)1148
JournalCommunications Biology
Volume4
Issue number1
DOIs
Publication statusPublished - 7 Oct 2021

Bibliographical note

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).

Other keywords

  • Ear, Inner/growth & development
  • Genome, Human
  • Genome-Wide Association Study
  • Humans
  • Labyrinth Diseases/genetics
  • Mutation, Missense
  • Vertigo/genetics

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