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


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.

SUBMITTER: Skuladottir AT 

PROVIDER: S-EPMC8497462 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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

Skuladottir Astros Th AT   Bjornsdottir Gyda G   Nawaz Muhammad Sulaman MS   Petersen Hannes H   Rognvaldsson Solvi S   Moore Kristjan Helgi Swerford KHS   Olafsson Pall I PI   Magnusson Sigurður H SH   Bjornsdottir Anna A   Sveinsson Olafur A OA   Sigurdardottir Gudrun R GR   Saevarsdottir Saedis S   Ivarsdottir Erna V EV   Stefansdottir Lilja L   Gunnarsson Bjarni B   Muhlestein Joseph B JB   Knowlton Kirk U KU   Jones David A DA   Nadauld Lincoln D LD   Hartmann Annette M AM   Rujescu Dan D   Strupp Michael M   Walters G Bragi GB   Thorgeirsson Thorgeir E TE   Jonsdottir Ingileif I   Holm Hilma H   Thorleifsson Gudmar G   Gudbjartsson Daniel F DF   Sulem Patrick P   Stefansson Hreinn H   Stefansson Kari K  

Communications biology 20211007 1


Vertigo is the leading symptom of vestibular disorders and a major risk factor for falls. In a genome-wide association study of vertigo (N<sub>cases</sub> = 48,072, N<sub>controls</sub> = 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 position  ...[more]

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