A genome-wide association study for age-related hearing impairment in the Saami
Abstract This study aimed to contribute to the elucidation of the genetic basis of age-related hearing impairment (ARHI), a common multifactorial disease with an important genetic contribution as demonstrated by heritability studies. We conducted a genome-wide association study (GWAS) in the Finnish...
Published in: | European Journal of Human Genetics |
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Language: | English |
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Nature Publishing Group
2010
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Online Access: | http://hdl.handle.net/2262/44667 https://doi.org/10.1038/ejhg.2009.234 |
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fttrinitycoll:oai:tara.tcd.ie:2262/44667 |
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openpolar |
institution |
Open Polar |
collection |
The University of Dublin, Trinity College: TARA (Trinity's Access to Research Archive) |
op_collection_id |
fttrinitycoll |
language |
English |
topic |
genome-wide association study age-related hearing impairment Saami |
spellingShingle |
genome-wide association study age-related hearing impairment Saami A genome-wide association study for age-related hearing impairment in the Saami |
topic_facet |
genome-wide association study age-related hearing impairment Saami |
description |
Abstract This study aimed to contribute to the elucidation of the genetic basis of age-related hearing impairment (ARHI), a common multifactorial disease with an important genetic contribution as demonstrated by heritability studies. We conducted a genome-wide association study (GWAS) in the Finnish Saami, a small ancient genetically isolated population without evidence of demographic expansion. The choice of this study population was motivated by its anticipated higher extent of linkage disequilibrium, potentially offering a substantial power advantage for association mapping. DNA samples and audiometric measurements were collected from 352 Finnish Saami individuals, aged between 50 and 75 years. To reduce the multiple testing burden, we applied principal component analysis to the multivariate audiometric phenotype. The first three principal components (PC) captured 80% of the variation in hearing thresholds, while maintaining biologically important audiometric features. All subjects were genotyped with the Affymetrix 100K chip. To account for multiple levels of relatedness among subjects, as well as population stratification, association testing was performed using a mixed model. We summarized top-ranking association signals for the three traits under study. The top-ranked SNP, rs457717 (P-value 3.55x10-7), was associated with PC3 and was localised in an intron of the IQ motif-containing GTPase-activating-like protein (IQGAP2). Intriguingly, SNP rs161927 (P-value 0.000149), seventh-ranked for PC1, was positioned immediately downstream of the metabotropic glutamate receptor 7 gene (GRM7). As a previous GWAS in a European and a Finnish sample set already suggested a role for GRM7 in ARHI, this study provides further evidence for the involvement of this gene. guy.vancamp@ua.ac.be (Van Camp, Guy) Department of Medical Genetics - Universiteitsplein 1, Antwerpen, Antwerpen B-2610--> - BELGIUM (Van Camp, Guy) Department of Medical Genetics - Universiteitsplein 1, Antwerpen, Antwerpen B-2610--> - BELGIUM (Van Laer, Lut) Department of Medical Genetics - Universiteitsplein 1, Antwerpen, Antwerpen B-2610--> - BELGIUM (Huyghe, Jeroen) Department of Medical Genetics - Universiteitsplein 1, Antwerpen, Antwerpen B-2610--> - BELGIUM (Hannula, Samuli) Department of Medical Genetics - Universiteitsplein 1, Antwerpen, Antwerpen B-2610--> - BELGIUM (Van Eyken, Els) Department of Medical Genetics - Universiteitsplein 1, Antwerpen, Antwerpen B-2610--> - BELGIUM (Stephan, Dietrich) Department of Medical Genetics - Universiteitsplein 1, Antwerpen, Antwerpen B-2610--> - BELGIUM (Maki-Torkko, Elina) Department of Medical Genetics - Universiteitsplein 1, Antwerpen, Antwerpen B-2610--> - BELGIUM (Aikio, Pekka) Department of Medical Genetics - Universiteitsplein 1, Antwerpen, Antwerpen B-2610--> - BELGIUM (Lysholm-Bernacchi, Alana) Department of Medical Genetics - Universiteitsplein 1, Antwerpen, Antwerpen B-2610--> - BELGIUM (Sorri, Martti) Department of Medical Genetics - Universiteitsplein 1, Antwerpen, Antwerpen B-2610--> - BELGIUM (Huentelman, Matthew J) Department of Medical Genetics - Universiteitsplein 1, Antwerpen, Antwerpen B-2610--> - BELGIUM (Fransen, Erik) BELGIUM Accepted: 2009-12-01 Received: 2009-02-23 Revised: 2009-09-15 |
title |
A genome-wide association study for age-related hearing impairment in the Saami |
title_short |
A genome-wide association study for age-related hearing impairment in the Saami |
title_full |
A genome-wide association study for age-related hearing impairment in the Saami |
title_fullStr |
A genome-wide association study for age-related hearing impairment in the Saami |
title_full_unstemmed |
A genome-wide association study for age-related hearing impairment in the Saami |
title_sort |
genome-wide association study for age-related hearing impairment in the saami |
publisher |
Nature Publishing Group |
publishDate |
2010 |
url |
http://hdl.handle.net/2262/44667 https://doi.org/10.1038/ejhg.2009.234 |
long_lat |
ENVELOPE(23.816,23.816,66.180,66.180) ENVELOPE(-179.078,-179.078,67.632,67.632) ENVELOPE(26.717,26.717,67.683,67.683) ENVELOPE(163.850,163.850,-77.483,-77.483) ENVELOPE(25.481,25.481,68.370,68.370) |
geographic |
Pekka Maki Aikio Bernacchi Hannula |
geographic_facet |
Pekka Maki Aikio Bernacchi Hannula |
genre |
saami |
genre_facet |
saami |
op_relation |
1018-4813 (pISSN) 1018-4813.121-09-EJHG 121-09-EJHGR (manuscript) http://hdl.handle.net/2262/44667 European Journal of Human Genetics n/a doi:10.1038/ejhg.2009.234 ejhg (publisher-id) |
op_rights |
Copyright ? 2009, European Journal of Human Genetics 6 months |
op_doi |
https://doi.org/10.1038/ejhg.2009.234 |
container_title |
European Journal of Human Genetics |
container_volume |
18 |
container_issue |
6 |
container_start_page |
685 |
op_container_end_page |
693 |
_version_ |
1766180506787905536 |
spelling |
fttrinitycoll:oai:tara.tcd.ie:2262/44667 2023-05-15T18:08:14+02:00 A genome-wide association study for age-related hearing impairment in the Saami 2010-12-14T22:20:23Z http://hdl.handle.net/2262/44667 https://doi.org/10.1038/ejhg.2009.234 en eng Nature Publishing Group 1018-4813 (pISSN) 1018-4813.121-09-EJHG 121-09-EJHGR (manuscript) http://hdl.handle.net/2262/44667 European Journal of Human Genetics n/a doi:10.1038/ejhg.2009.234 ejhg (publisher-id) Copyright ? 2009, European Journal of Human Genetics 6 months genome-wide association study age-related hearing impairment Saami 2010 fttrinitycoll https://doi.org/10.1038/ejhg.2009.234 2020-02-16T13:49:58Z Abstract This study aimed to contribute to the elucidation of the genetic basis of age-related hearing impairment (ARHI), a common multifactorial disease with an important genetic contribution as demonstrated by heritability studies. We conducted a genome-wide association study (GWAS) in the Finnish Saami, a small ancient genetically isolated population without evidence of demographic expansion. The choice of this study population was motivated by its anticipated higher extent of linkage disequilibrium, potentially offering a substantial power advantage for association mapping. DNA samples and audiometric measurements were collected from 352 Finnish Saami individuals, aged between 50 and 75 years. To reduce the multiple testing burden, we applied principal component analysis to the multivariate audiometric phenotype. The first three principal components (PC) captured 80% of the variation in hearing thresholds, while maintaining biologically important audiometric features. All subjects were genotyped with the Affymetrix 100K chip. To account for multiple levels of relatedness among subjects, as well as population stratification, association testing was performed using a mixed model. We summarized top-ranking association signals for the three traits under study. The top-ranked SNP, rs457717 (P-value 3.55x10-7), was associated with PC3 and was localised in an intron of the IQ motif-containing GTPase-activating-like protein (IQGAP2). Intriguingly, SNP rs161927 (P-value 0.000149), seventh-ranked for PC1, was positioned immediately downstream of the metabotropic glutamate receptor 7 gene (GRM7). As a previous GWAS in a European and a Finnish sample set already suggested a role for GRM7 in ARHI, this study provides further evidence for the involvement of this gene. guy.vancamp@ua.ac.be (Van Camp, Guy) Department of Medical Genetics - Universiteitsplein 1, Antwerpen, Antwerpen B-2610--> - BELGIUM (Van Camp, Guy) Department of Medical Genetics - Universiteitsplein 1, Antwerpen, Antwerpen B-2610--> - BELGIUM (Van Laer, Lut) Department of Medical Genetics - Universiteitsplein 1, Antwerpen, Antwerpen B-2610--> - BELGIUM (Huyghe, Jeroen) Department of Medical Genetics - Universiteitsplein 1, Antwerpen, Antwerpen B-2610--> - BELGIUM (Hannula, Samuli) Department of Medical Genetics - Universiteitsplein 1, Antwerpen, Antwerpen B-2610--> - BELGIUM (Van Eyken, Els) Department of Medical Genetics - Universiteitsplein 1, Antwerpen, Antwerpen B-2610--> - BELGIUM (Stephan, Dietrich) Department of Medical Genetics - Universiteitsplein 1, Antwerpen, Antwerpen B-2610--> - BELGIUM (Maki-Torkko, Elina) Department of Medical Genetics - Universiteitsplein 1, Antwerpen, Antwerpen B-2610--> - BELGIUM (Aikio, Pekka) Department of Medical Genetics - Universiteitsplein 1, Antwerpen, Antwerpen B-2610--> - BELGIUM (Lysholm-Bernacchi, Alana) Department of Medical Genetics - Universiteitsplein 1, Antwerpen, Antwerpen B-2610--> - BELGIUM (Sorri, Martti) Department of Medical Genetics - Universiteitsplein 1, Antwerpen, Antwerpen B-2610--> - BELGIUM (Huentelman, Matthew J) Department of Medical Genetics - Universiteitsplein 1, Antwerpen, Antwerpen B-2610--> - BELGIUM (Fransen, Erik) BELGIUM Accepted: 2009-12-01 Received: 2009-02-23 Revised: 2009-09-15 Other/Unknown Material saami The University of Dublin, Trinity College: TARA (Trinity's Access to Research Archive) Pekka ENVELOPE(23.816,23.816,66.180,66.180) Maki ENVELOPE(-179.078,-179.078,67.632,67.632) Aikio ENVELOPE(26.717,26.717,67.683,67.683) Bernacchi ENVELOPE(163.850,163.850,-77.483,-77.483) Hannula ENVELOPE(25.481,25.481,68.370,68.370) European Journal of Human Genetics 18 6 685 693 |