The genetic architecture of age-related hearing impairment revealed by genome-wide association analysis
Abstract 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 ad...
Published in: | Communications Biology |
---|---|
Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Springer Science and Business Media LLC
2021
|
Subjects: | |
Online Access: | http://dx.doi.org/10.1038/s42003-021-02224-9 http://www.nature.com/articles/s42003-021-02224-9.pdf http://www.nature.com/articles/s42003-021-02224-9 |
id |
crspringernat:10.1038/s42003-021-02224-9 |
---|---|
record_format |
openpolar |
spelling |
crspringernat:10.1038/s42003-021-02224-9 2023-05-15T16:50:16+02:00 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 2021 http://dx.doi.org/10.1038/s42003-021-02224-9 http://www.nature.com/articles/s42003-021-02224-9.pdf http://www.nature.com/articles/s42003-021-02224-9 en eng Springer Science and Business Media LLC https://creativecommons.org/licenses/by/4.0 https://creativecommons.org/licenses/by/4.0 CC-BY Communications Biology volume 4, issue 1 ISSN 2399-3642 General Agricultural and Biological Sciences General Biochemistry, Genetics and Molecular Biology Medicine (miscellaneous) journal-article 2021 crspringernat https://doi.org/10.1038/s42003-021-02224-9 2022-01-04T15:42:53Z Abstract 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. Article in Journal/Newspaper Iceland Springer Nature (via Crossref) Communications Biology 4 1 |
institution |
Open Polar |
collection |
Springer Nature (via Crossref) |
op_collection_id |
crspringernat |
language |
English |
topic |
General Agricultural and Biological Sciences General Biochemistry, Genetics and Molecular Biology Medicine (miscellaneous) |
spellingShingle |
General Agricultural and Biological Sciences General Biochemistry, Genetics and Molecular Biology Medicine (miscellaneous) 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 |
topic_facet |
General Agricultural and Biological Sciences General Biochemistry, Genetics and Molecular Biology Medicine (miscellaneous) |
description |
Abstract 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 |
Article in Journal/Newspaper |
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. |
title |
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_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_sort |
genetic architecture of age-related hearing impairment revealed by genome-wide association analysis |
publisher |
Springer Science and Business Media LLC |
publishDate |
2021 |
url |
http://dx.doi.org/10.1038/s42003-021-02224-9 http://www.nature.com/articles/s42003-021-02224-9.pdf http://www.nature.com/articles/s42003-021-02224-9 |
genre |
Iceland |
genre_facet |
Iceland |
op_source |
Communications Biology volume 4, issue 1 ISSN 2399-3642 |
op_rights |
https://creativecommons.org/licenses/by/4.0 https://creativecommons.org/licenses/by/4.0 |
op_rightsnorm |
CC-BY |
op_doi |
https://doi.org/10.1038/s42003-021-02224-9 |
container_title |
Communications Biology |
container_volume |
4 |
container_issue |
1 |
_version_ |
1766040433826201600 |