Genetic architecture distinguishes tinnitus from hearing loss

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Tinnitus is a heritable, highly prevalent auditory disorder treated by multiple medical specialties. Previous GWAS indicated high genetic correlations between tinnitus and hearing loss, with little indication of differentiating signals. We present a GWAS meta-analysis, triple previous sample sizes, and expand to non-European ancestries. GWAS in 596,905 Million Veteran Program subjects identified 39 tinnitus loci, and identified genes related to neuronal synapses and cochlear structural support. Applying state-of-the-art analytic tools, we confirm a large number of shared variants, but also a distinct genetic architecture of tinnitus, with higher polygenicity and large proportion of variants not shared with hearing difficulty. Tissue-expression analysis for tinnitus infers broad enrichment across most brain tissues, in contrast to hearing difficulty. Finally, tinnitus is not only correlated with hearing loss, but also with a spectrum of psychiatric disorders, providing potential new avenues for treatment. This study establishes tinnitus as a distinct disorder separate from hearing difficulties.

Abstract

The genetic basis of tinnitus and how it relates to hearing loss genetics is unknown. In a large GWAS for tinnitus, the authors discover tinnitus’ distinct genetic architecture from hearing loss and its correlation with a spectrum of psychiatric disorders.

Related collections

Most cited references 111

Record: found
Abstract: found
Article: found

Is Open Access

A global reference for human genetic variation

Lachlan Coin, Robert Garry, Oleksyk Taras (2018)

The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.

0 comments Cited 4382 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Second-generation PLINK: rising to the challenge of larger and richer datasets

Christopher Chang, Carson Chow, Laurent Tellier … (2015)

PLINK 1 is a widely used open-source C/C++ toolset for genome-wide association studies (GWAS) and research in population genetics. However, the steady accumulation of data from imputation and whole-genome sequencing studies has exposed a strong need for even faster and more scalable implementations of key functions. In addition, GWAS and population-genetic data now frequently contain probabilistic calls, phase information, and/or multiallelic variants, none of which can be represented by PLINK 1's primary data format. To address these issues, we are developing a second-generation codebase for PLINK. The first major release from this codebase, PLINK 1.9, introduces extensive use of bit-level parallelism, O(sqrt(n))-time/constant-space Hardy-Weinberg equilibrium and Fisher's exact tests, and many other algorithmic improvements. In combination, these changes accelerate most operations by 1-4 orders of magnitude, and allow the program to handle datasets too large to fit in RAM. This will be followed by PLINK 2.0, which will introduce (a) a new data format capable of efficiently representing probabilities, phase, and multiallelic variants, and (b) extensions of many functions to account for the new types of information. The second-generation versions of PLINK will offer dramatic improvements in performance and compatibility. For the first time, users without access to high-end computing resources can perform several essential analyses of the feature-rich and very large genetic datasets coming into use.

0 comments Cited 3099 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Spatial reconstruction of single-cell gene expression

Rahul Satija, Jeffrey A Farrell, David Gennert … (2015)

Spatial localization is a key determinant of cellular fate and behavior, but spatial RNA assays traditionally rely on staining for a limited number of RNA species. In contrast, single-cell RNA-seq allows for deep profiling of cellular gene expression, but established methods separate cells from their native spatial context. Here we present Seurat, a computational strategy to infer cellular localization by integrating single-cell RNA-seq data with in situ RNA patterns. We applied Seurat to spatially map 851 single cells from dissociated zebrafish (Danio rerio) embryos, inferring a transcriptome-wide map of spatial patterning. We confirmed Seurat’s accuracy using several experimental approaches, and used it to identify a set of archetypal expression patterns and spatial markers. Additionally, Seurat correctly localizes rare subpopulations, accurately mapping both spatially restricted and scattered groups. Seurat will be applicable to mapping cellular localization within complex patterned tissues in diverse systems.

0 comments Cited 1810 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Royce E. Clifford:

ORCID: http://orcid.org/0000-0002-5515-4336

r2clifford@health.ucsd.edu

Caroline M. Nievergelt:

ORCID: http://orcid.org/0000-0001-5766-8923

cnievergelt@health.ucsd.edu

Journal

Journal ID (nlm-ta): Nat Commun

Journal ID (iso-abbrev): Nat Commun

Title: Nature Communications

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2041-1723

Publication date (Electronic): 19 January 2024

Publication date PMC-release: 19 January 2024

Publication date Collection: 2024

Volume: 15

Electronic Location Identifier: 614

Affiliations

[1 ]GRID grid.410371.0, ISNI 0000 0004 0419 2708, Veterans Affairs San Diego Healthcare System, Research Service, ; San Diego, CA USA

[2 ]University of California San Diego, Division of Otolaryngology – Head and Neck Surgery, ( https://ror.org/0168r3w48) La Jolla, CA USA

[3 ]University of California San Diego, Department of Psychiatry, ( https://ror.org/0168r3w48) La Jolla, CA USA

[4 ]GRID grid.38142.3c, ISNI 000000041936754X, Harvard Medical School, Department of Psychiatry, ; Boston, MA USA

[5 ]McLean Hospital, Center of Excellence in Depression and Anxiety Disorders, ( https://ror.org/01kta7d96) Belmont, MA USA

[6 ]King’s College London, NIHR Maudsley BRC, ( https://ror.org/0220mzb33) London, UK

[7 ]King’s College London, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, ( https://ror.org/0220mzb33) London, UK

[8 ]GRID grid.410371.0, ISNI 0000 0004 0419 2708, Veterans Affairs San Diego Healthcare System, Psychiatry Service, ; San Diego, CA USA

[9 ]University of California San Diego, School of Public Health, ( https://ror.org/0168r3w48) La Jolla, CA USA

[10 ]VA Palo Alto Health Care System, ( https://ror.org/00nr17z89) Palo Alto, CA USA

Author information

Royce E. Clifford http://orcid.org/0000-0002-5515-4336

Jonathan R. I. Coleman http://orcid.org/0000-0002-6759-0944

Nikolaos P. Daskalakis http://orcid.org/0000-0003-1660-9112

Elizabeth A. Mikita http://orcid.org/0000-0002-2113-8274

Murray B. Stein http://orcid.org/0000-0001-9564-2871

Francesca Telese http://orcid.org/0000-0003-3877-0628

Caroline M. Nievergelt http://orcid.org/0000-0001-5766-8923

Article

Publisher ID: 44842

DOI: 10.1038/s41467-024-44842-x

PMC ID: 10799010

PubMed ID: 38242899

SO-VID: 4798aa2b-8ad8-45a8-9e93-e79b7da480e7

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 20 June 2023

Date accepted : 4 January 2024

Funding

Funded by: FundRef https://doi.org/10.13039/100000738, U.S. Department of Veterans Affairs (Department of Veterans Affairs);

Award ID: RX004293

Award ID: BX005920

Award Recipient : Royce E. Clifford Caroline M. Nievergelt

Custom metadata

ScienceOpen disciplines: Uncategorized

Keywords: genome-wide association studies,diseases,predictive markers

Data availability:

ScienceOpen disciplines: Uncategorized

Keywords: genome-wide association studies, diseases, predictive markers

Genetic architecture distinguishes tinnitus from hearing loss

Read this article at

Abstract

Abstract

Related collections

Genes & Diseases

Most cited references 111

A global reference for human genetic variation

Second-generation PLINK: rising to the challenge of larger and richer datasets

Spatial reconstruction of single-cell gene expression

Author and article information

Contributors

Journal

Affiliations

Author information

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 305

Cited by 1

Most referenced authors 7,031