Genome-Wide Association Study for Age-Related Hearing Loss (AHL) in the Mouse: A Meta-Analysis

AbstractVertigo 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.

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Insights into the Genetic Architecture of Early Stage Age-Related Macular Degeneration: A Genome-Wide Association Study Meta-Analysis

PLoS ONE ◽

10.1371/journal.pone.0053830 ◽

2013 ◽

Vol 8 (1) ◽

pp. e53830 ◽

Cited By ~ 66

Author(s):

Elizabeth G. Holliday ◽

Albert V. Smith ◽

Belinda K. Cornes ◽

Gabriëlle H. S. Buitendijk ◽

Richard A. Jensen ◽

...

Keyword(s):

Association Study ◽

Genetic Architecture ◽

Genome Wide Association Study ◽

Early Stage ◽

Meta Analysis ◽

Age Related Macular Degeneration ◽

Genome Wide Association ◽

Age Related ◽

Genome Wide ◽

A Genome

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Genome-wide association study meta-analysis identifies the SOAT1/AXDND1 locus to be associated with hip and forearm fracture risk

Bone Abstracts ◽

10.1530/boneabs.1.pp279 ◽

2013 ◽

Author(s):

Ulrika Pettersson-Kymmer ◽

Andrea Lacroix ◽

Joel Eriksson ◽

Ulrica Bergstrom ◽

Beatrice Melin ◽

...

Keyword(s):

Fracture Risk ◽

Association Study ◽

Genome Wide Association Study ◽

Meta Analysis ◽

Forearm Fracture ◽

Genome Wide Association ◽

Genome Wide

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Faculty Opinions recommendation of Risk loci for chronic obstructive pulmonary disease: a genome-wide association study and meta-analysis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718310292.793531798 ◽

2017 ◽

Author(s):

Erik Melen

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Association Study ◽

Pulmonary Disease ◽

Genome Wide Association Study ◽

Meta Analysis ◽

Genome Wide Association ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Genome Wide ◽

A Genome

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Expanded Genome-Wide Association Study Meta-Analysis of Psoriasis Expands the Catalog of Common Psoriasis-Associated Variants

Journal of Investigative Dermatology Symposium Proceedings ◽

10.1016/j.jisp.2018.09.005 ◽

2018 ◽

Vol 19 (2) ◽

pp. S77-S78 ◽

Cited By ~ 9

Author(s):

James T. Elder

Keyword(s):

Association Study ◽

Genome Wide Association Study ◽

Meta Analysis ◽

Genome Wide Association ◽

Genome Wide

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Genome-Wide Association Meta-Analysis Supports Genes Involved in Valve and Cardiac Development to Associate With Mitral Valve Prolapse

Circulation Genomic and Precision Medicine ◽

10.1161/circgen.120.003148 ◽

2021 ◽

Author(s):

Mengyao Yu ◽

Sergiy Kyryachenko ◽

Stephanie Debette ◽

Philippe Amouyel ◽

Jean-Jacques Schott ◽

...

Keyword(s):

Mitral Valve ◽

Association Study ◽

Genome Wide Association Study ◽

Cardiac Development ◽

Meta Analysis ◽

Genome Wide Association ◽

Uk Biobank ◽

Additional Risk ◽

Genome Wide ◽

The Uk

Background: Mitral valve prolapse (MVP) is a common cardiac valve disease, which affects 1 in 40 in the general population. Previous genome-wide association study have identified 6 risk loci for MVP. But these loci explained only partially the genetic risk for MVP. We aim to identify additional risk loci for MVP by adding data set from the UK Biobank. Methods: We reanalyzed 1007/479 cases from the MVP-France study, 1469/862 controls from the MVP-Nantes study for reimputation genotypes using HRC and TOPMed panels. We also incorporated 434 MVP cases and 4527 controls from the UK Biobank for discovery analyses. Genetic association was conducted using SNPTEST and meta-analyses using METAL. We used FUMA for post-genome-wide association study annotations and MAGMA for gene-based and gene-set analyses. Results: We found TOPMed imputation to perform better in terms of accuracy in the lower ranges of minor allele frequency below 0.1. Our updated meta-analysis included UK Biobank study for ≈8 million common single-nucleotide polymorphisms (minor allele frequency >0.01) and replicated the association on Chr2 as the top association signal near TNS1 . We identified an additional risk locus on Chr1 ( SYT2 ) and 2 suggestive risk loci on chr8 ( MSRA ) and chr19 ( FBXO46 ), all driven by common variants. Gene-based association using MAGMA revealed 6 risk genes for MVP with pronounced expression levels in cardiovascular tissues, especially the heart and globally part of enriched GO terms related to cardiac development. Conclusions: We report an updated meta-analysis genome-wide association study for MVP using dense imputation coverage and an improved case-control sample. We describe several loci and genes with MVP spanning biological mechanisms highly relevant to MVP, especially during valve and heart development.

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