Cargando…
The genetic architecture of age-related hearing impairment revealed by genome-wide association analysis
Age-related hearing impairment (ARHI) is the most common sensory disorder in older adults. We conducted a genome-wide association meta-analysis of 121,934 ARHI cases and 591,699 controls from Iceland and the UK. We identified 21 novel sequence variants, of which 13 are rare, under either additive or...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2021
|
| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190123/ https://www.ncbi.nlm.nih.gov/pubmed/34108613 http://dx.doi.org/10.1038/s42003-021-02224-9 |
| _version_ | 1783705629254221824 |
|---|---|
| author | Ivarsdottir, Erna V. Holm, Hilma Benonisdottir, Stefania Olafsdottir, Thorhildur Sveinbjornsson, Gardar Thorleifsson, Gudmar Eggertsson, Hannes P. Halldorsson, Gisli H. Hjorleifsson, Kristjan E. Melsted, Pall Gylfason, Arnaldur Arnadottir, Gudny A. Oddsson, Asmundur Jensson, Brynjar O. Jonasdottir, Aslaug Jonasdottir, Adalbjorg Juliusdottir, Thorhildur Stefansdottir, Lilja Tragante, Vinicius Halldorsson, Bjarni V. Petersen, Hannes Thorgeirsson, Gudmundur Thorsteinsdottir, Unnur Sulem, Patrick Hinriksdottir, Ingibjorg Jonsdottir, Ingileif Gudbjartsson, Daniel F. Stefansson, Kari |
| author_facet | Ivarsdottir, Erna V. Holm, Hilma Benonisdottir, Stefania Olafsdottir, Thorhildur Sveinbjornsson, Gardar Thorleifsson, Gudmar Eggertsson, Hannes P. Halldorsson, Gisli H. Hjorleifsson, Kristjan E. Melsted, Pall Gylfason, Arnaldur Arnadottir, Gudny A. Oddsson, Asmundur Jensson, Brynjar O. Jonasdottir, Aslaug Jonasdottir, Adalbjorg Juliusdottir, Thorhildur Stefansdottir, Lilja Tragante, Vinicius Halldorsson, Bjarni V. Petersen, Hannes Thorgeirsson, Gudmundur Thorsteinsdottir, Unnur Sulem, Patrick Hinriksdottir, Ingibjorg Jonsdottir, Ingileif Gudbjartsson, Daniel F. Stefansson, Kari |
| author_sort | Ivarsdottir, Erna V. |
| collection | PubMed |
| description | Age-related hearing impairment (ARHI) is the most common sensory disorder in older adults. We conducted a genome-wide association meta-analysis of 121,934 ARHI cases and 591,699 controls from Iceland and the UK. We identified 21 novel sequence variants, of which 13 are rare, under either additive or recessive models. Of special interest are a missense variant in LOXHD1 (MAF = 1.96%) and a tandem duplication in FBF1 covering 4 exons (MAF = 0.22%) associating with ARHI (OR = 3.7 for homozygotes, P = 1.7 × 10(−22) and OR = 4.2 for heterozygotes, P = 5.7 × 10(−27), respectively). We constructed an ARHI genetic risk score (GRS) using common variants and showed that a common variant GRS can identify individuals at risk comparable to carriers of rare high penetrance variants. Furthermore, we found that ARHI and tinnitus share genetic causes. This study sheds a new light on the genetic architecture of ARHI, through several rare variants in both Mendelian deafness genes and genes not previously linked to hearing. |
| format | Online Article Text |
| id | pubmed-8190123 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2021 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-81901232021-06-28 The genetic architecture of age-related hearing impairment revealed by genome-wide association analysis Ivarsdottir, Erna V. Holm, Hilma Benonisdottir, Stefania Olafsdottir, Thorhildur Sveinbjornsson, Gardar Thorleifsson, Gudmar Eggertsson, Hannes P. Halldorsson, Gisli H. Hjorleifsson, Kristjan E. Melsted, Pall Gylfason, Arnaldur Arnadottir, Gudny A. Oddsson, Asmundur Jensson, Brynjar O. Jonasdottir, Aslaug Jonasdottir, Adalbjorg Juliusdottir, Thorhildur Stefansdottir, Lilja Tragante, Vinicius Halldorsson, Bjarni V. Petersen, Hannes Thorgeirsson, Gudmundur Thorsteinsdottir, Unnur Sulem, Patrick Hinriksdottir, Ingibjorg Jonsdottir, Ingileif Gudbjartsson, Daniel F. Stefansson, Kari Commun Biol Article Age-related hearing impairment (ARHI) is the most common sensory disorder in older adults. We conducted a genome-wide association meta-analysis of 121,934 ARHI cases and 591,699 controls from Iceland and the UK. We identified 21 novel sequence variants, of which 13 are rare, under either additive or recessive models. Of special interest are a missense variant in LOXHD1 (MAF = 1.96%) and a tandem duplication in FBF1 covering 4 exons (MAF = 0.22%) associating with ARHI (OR = 3.7 for homozygotes, P = 1.7 × 10(−22) and OR = 4.2 for heterozygotes, P = 5.7 × 10(−27), respectively). We constructed an ARHI genetic risk score (GRS) using common variants and showed that a common variant GRS can identify individuals at risk comparable to carriers of rare high penetrance variants. Furthermore, we found that ARHI and tinnitus share genetic causes. This study sheds a new light on the genetic architecture of ARHI, through several rare variants in both Mendelian deafness genes and genes not previously linked to hearing. Nature Publishing Group UK 2021-06-09 /pmc/articles/PMC8190123/ /pubmed/34108613 http://dx.doi.org/10.1038/s42003-021-02224-9 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
| spellingShingle | Article Ivarsdottir, Erna V. Holm, Hilma Benonisdottir, Stefania Olafsdottir, Thorhildur Sveinbjornsson, Gardar Thorleifsson, Gudmar Eggertsson, Hannes P. Halldorsson, Gisli H. Hjorleifsson, Kristjan E. Melsted, Pall Gylfason, Arnaldur Arnadottir, Gudny A. Oddsson, Asmundur Jensson, Brynjar O. Jonasdottir, Aslaug Jonasdottir, Adalbjorg Juliusdottir, Thorhildur Stefansdottir, Lilja Tragante, Vinicius Halldorsson, Bjarni V. Petersen, Hannes Thorgeirsson, Gudmundur Thorsteinsdottir, Unnur Sulem, Patrick Hinriksdottir, Ingibjorg Jonsdottir, Ingileif Gudbjartsson, Daniel F. Stefansson, Kari The genetic architecture of age-related hearing impairment revealed by genome-wide association analysis |
| title | The genetic architecture of age-related hearing impairment revealed by genome-wide association analysis |
| title_full | The genetic architecture of age-related hearing impairment revealed by genome-wide association analysis |
| title_fullStr | The genetic architecture of age-related hearing impairment revealed by genome-wide association analysis |
| title_full_unstemmed | The genetic architecture of age-related hearing impairment revealed by genome-wide association analysis |
| title_short | The genetic architecture of age-related hearing impairment revealed by genome-wide association analysis |
| title_sort | genetic architecture of age-related hearing impairment revealed by genome-wide association analysis |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190123/ https://www.ncbi.nlm.nih.gov/pubmed/34108613 http://dx.doi.org/10.1038/s42003-021-02224-9 |
| work_keys_str_mv | AT ivarsdottirernav thegeneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT holmhilma thegeneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT benonisdottirstefania thegeneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT olafsdottirthorhildur thegeneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT sveinbjornssongardar thegeneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT thorleifssongudmar thegeneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT eggertssonhannesp thegeneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT halldorssongislih thegeneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT hjorleifssonkristjane thegeneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT melstedpall thegeneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT gylfasonarnaldur thegeneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT arnadottirgudnya thegeneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT oddssonasmundur thegeneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT jenssonbrynjaro thegeneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT jonasdottiraslaug thegeneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT jonasdottiradalbjorg thegeneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT juliusdottirthorhildur thegeneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT stefansdottirlilja thegeneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT tragantevinicius thegeneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT halldorssonbjarniv thegeneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT petersenhannes thegeneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT thorgeirssongudmundur thegeneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT thorsteinsdottirunnur thegeneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT sulempatrick thegeneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT hinriksdottiringibjorg thegeneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT jonsdottiringileif thegeneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT gudbjartssondanielf thegeneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT stefanssonkari thegeneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT ivarsdottirernav geneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT holmhilma geneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT benonisdottirstefania geneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT olafsdottirthorhildur geneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT sveinbjornssongardar geneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT thorleifssongudmar geneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT eggertssonhannesp geneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT halldorssongislih geneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT hjorleifssonkristjane geneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT melstedpall geneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT gylfasonarnaldur geneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT arnadottirgudnya geneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT oddssonasmundur geneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT jenssonbrynjaro geneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT jonasdottiraslaug geneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT jonasdottiradalbjorg geneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT juliusdottirthorhildur geneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT stefansdottirlilja geneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT tragantevinicius geneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT halldorssonbjarniv geneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT petersenhannes geneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT thorgeirssongudmundur geneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT thorsteinsdottirunnur geneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT sulempatrick geneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT hinriksdottiringibjorg geneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT jonsdottiringileif geneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT gudbjartssondanielf geneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis AT stefanssonkari geneticarchitectureofagerelatedhearingimpairmentrevealedbygenomewideassociationanalysis |