Genome-wide SNP-based linkage scan identifies a locus on 8q24 for an age-related hearing impairment trait

Jeroen R Huyghe; Lut Van Laer; Jan-Jaap Hendrickx; Erik Fransen; Kelly Demeester; Vedat Topsakal; Sylvia Kunst; Minna Manninen; Mona Jensen; Amanda Bonaconsa; Manuela Mazzoli; Manuela Baur; Samuli Hannula; Elina Mäki-Torkko; Angeles Espeso; Els Van Eyken; Antonia Flaquer; Christian Becker; Dafydd Stephens; Martti Sorri; Eva Orzan; Michael Bille; Agnete Parving; Ilmari Pyykkö; Cor W R J Cremers; Hannie Kremer; Paul H Van de Heyning; Thomas F Wienker; Peter Nürnberg; Markus Pfister; Guy Van Camp

doi:10.1016/j.ajhg.2008.08.002

Genome-wide SNP-based linkage scan identifies a locus on 8q24 for an age-related hearing impairment trait

Jeroen R Huyghe, Lut Van Laer, Jan-Jaap Hendrickx, Erik Fransen, Kelly Demeester, Vedat Topsakal, Sylvia Kunst, Minna Manninen, Mona Jensen, Amanda Bonaconsa, Manuela Mazzoli, Manuela Baur, Samuli Hannula, Elina Mäki-Torkko, Angeles Espeso, Els Van Eyken, Antonia Flaquer, Christian Becker, Dafydd Stephens, Martti SorriEva Orzan, Michael Bille, Agnete Parving, Ilmari Pyykkö, Cor W R J Cremers, Hannie Kremer, Paul H Van de Heyning, Thomas F Wienker, Peter Nürnberg, Markus Pfister, Guy Van Camp

Research output: Contribution to journal › Article › peer-review

42 Citations (Scopus)

Abstract

Age-related hearing impairment (ARHI), or presbycusis, is a very common multifactorial disorder. Despite the knowledge that genetics play an important role in the etiology of human ARHI as revealed by heritability studies, to date, its precise genetic determinants remain elusive. Here we report the results of a cross-sectional family-based genetic study employing audiometric data. By using principal component analysis, we were able to reduce the dimensionality of this multivariate phenotype while capturing most of the variation and retaining biologically important features of the audiograms. We conducted a genome-wide association as well as a linkage scan with high-density SNP microarrays. Because of the presence of genetic population substructure, association testing was stratified after which evidence was combined by meta-analysis. No association signals reaching genome-wide significance were detected. Linkage analysis identified a linkage peak on 8q24.13-q24.22 for a trait correlated to audiogram shape. The signal reached genome-wide significance, as assessed by simulations. This finding represents the first locus for an ARHI trait.

Original language	English
Pages (from-to)	401-407
Number of pages	7
Journal	American Journal of Human Genetics
Volume	83
Issue number	3
DOIs	https://doi.org/10.1016/j.ajhg.2008.08.002
Publication status	Published - Sep 2008

Keywords

Aged
Aging/genetics
Chromosomes, Human, Pair 8/genetics
Cross-Sectional Studies
Female
Genetic Linkage
Genome, Human
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide
Presbycusis/genetics
Principal Component Analysis
Quantitative Trait Loci

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10.1016/j.ajhg.2008.08.002

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Huyghe, J. R., Van Laer, L., Hendrickx, J-J., Fransen, E., Demeester, K., Topsakal, V., Kunst, S., Manninen, M., Jensen, M., Bonaconsa, A., Mazzoli, M., Baur, M., Hannula, S., Mäki-Torkko, E., Espeso, A., Van Eyken, E., Flaquer, A., Becker, C., Stephens, D., ... Van Camp, G. (2008). Genome-wide SNP-based linkage scan identifies a locus on 8q24 for an age-related hearing impairment trait. American Journal of Human Genetics, 83(3), 401-407. https://doi.org/10.1016/j.ajhg.2008.08.002

Huyghe, Jeroen R ; Van Laer, Lut ; Hendrickx, Jan-Jaap ; Fransen, Erik ; Demeester, Kelly ; Topsakal, Vedat ; Kunst, Sylvia ; Manninen, Minna ; Jensen, Mona ; Bonaconsa, Amanda ; Mazzoli, Manuela ; Baur, Manuela ; Hannula, Samuli ; Mäki-Torkko, Elina ; Espeso, Angeles ; Van Eyken, Els ; Flaquer, Antonia ; Becker, Christian ; Stephens, Dafydd ; Sorri, Martti ; Orzan, Eva ; Bille, Michael ; Parving, Agnete ; Pyykkö, Ilmari ; Cremers, Cor W R J ; Kremer, Hannie ; Van de Heyning, Paul H ; Wienker, Thomas F ; Nürnberg, Peter ; Pfister, Markus ; Van Camp, Guy. / Genome-wide SNP-based linkage scan identifies a locus on 8q24 for an age-related hearing impairment trait. In: American Journal of Human Genetics. 2008 ; Vol. 83, No. 3. pp. 401-407.

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title = "Genome-wide SNP-based linkage scan identifies a locus on 8q24 for an age-related hearing impairment trait",

abstract = "Age-related hearing impairment (ARHI), or presbycusis, is a very common multifactorial disorder. Despite the knowledge that genetics play an important role in the etiology of human ARHI as revealed by heritability studies, to date, its precise genetic determinants remain elusive. Here we report the results of a cross-sectional family-based genetic study employing audiometric data. By using principal component analysis, we were able to reduce the dimensionality of this multivariate phenotype while capturing most of the variation and retaining biologically important features of the audiograms. We conducted a genome-wide association as well as a linkage scan with high-density SNP microarrays. Because of the presence of genetic population substructure, association testing was stratified after which evidence was combined by meta-analysis. No association signals reaching genome-wide significance were detected. Linkage analysis identified a linkage peak on 8q24.13-q24.22 for a trait correlated to audiogram shape. The signal reached genome-wide significance, as assessed by simulations. This finding represents the first locus for an ARHI trait.",

keywords = "Aged, Aging/genetics, Chromosomes, Human, Pair 8/genetics, Cross-Sectional Studies, Female, Genetic Linkage, Genome, Human, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Presbycusis/genetics, Principal Component Analysis, Quantitative Trait Loci",

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Huyghe, JR, Van Laer, L, Hendrickx, J-J, Fransen, E, Demeester, K, Topsakal, V, Kunst, S, Manninen, M, Jensen, M, Bonaconsa, A, Mazzoli, M, Baur, M, Hannula, S, Mäki-Torkko, E, Espeso, A, Van Eyken, E, Flaquer, A, Becker, C, Stephens, D, Sorri, M, Orzan, E, Bille, M, Parving, A, Pyykkö, I, Cremers, CWRJ, Kremer, H, Van de Heyning, PH, Wienker, TF, Nürnberg, P, Pfister, M & Van Camp, G 2008, 'Genome-wide SNP-based linkage scan identifies a locus on 8q24 for an age-related hearing impairment trait', American Journal of Human Genetics, vol. 83, no. 3, pp. 401-407. https://doi.org/10.1016/j.ajhg.2008.08.002

Genome-wide SNP-based linkage scan identifies a locus on 8q24 for an age-related hearing impairment trait. / Huyghe, Jeroen R; Van Laer, Lut; Hendrickx, Jan-Jaap; Fransen, Erik; Demeester, Kelly; Topsakal, Vedat; Kunst, Sylvia; Manninen, Minna; Jensen, Mona; Bonaconsa, Amanda; Mazzoli, Manuela; Baur, Manuela; Hannula, Samuli; Mäki-Torkko, Elina; Espeso, Angeles; Van Eyken, Els; Flaquer, Antonia; Becker, Christian; Stephens, Dafydd; Sorri, Martti; Orzan, Eva; Bille, Michael; Parving, Agnete; Pyykkö, Ilmari; Cremers, Cor W R J; Kremer, Hannie; Van de Heyning, Paul H; Wienker, Thomas F; Nürnberg, Peter; Pfister, Markus; Van Camp, Guy.

In: American Journal of Human Genetics, Vol. 83, No. 3, 09.2008, p. 401-407.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Genome-wide SNP-based linkage scan identifies a locus on 8q24 for an age-related hearing impairment trait

AU - Huyghe, Jeroen R

AU - Van Laer, Lut

AU - Hendrickx, Jan-Jaap

AU - Fransen, Erik

AU - Demeester, Kelly

AU - Topsakal, Vedat

AU - Kunst, Sylvia

AU - Manninen, Minna

AU - Jensen, Mona

AU - Bonaconsa, Amanda

AU - Mazzoli, Manuela

AU - Baur, Manuela

AU - Hannula, Samuli

AU - Mäki-Torkko, Elina

AU - Espeso, Angeles

AU - Van Eyken, Els

AU - Flaquer, Antonia

AU - Becker, Christian

AU - Stephens, Dafydd

AU - Sorri, Martti

AU - Orzan, Eva

AU - Bille, Michael

AU - Parving, Agnete

AU - Pyykkö, Ilmari

AU - Cremers, Cor W R J

AU - Kremer, Hannie

AU - Van de Heyning, Paul H

AU - Wienker, Thomas F

AU - Nürnberg, Peter

AU - Pfister, Markus

AU - Van Camp, Guy

PY - 2008/9

Y1 - 2008/9

N2 - Age-related hearing impairment (ARHI), or presbycusis, is a very common multifactorial disorder. Despite the knowledge that genetics play an important role in the etiology of human ARHI as revealed by heritability studies, to date, its precise genetic determinants remain elusive. Here we report the results of a cross-sectional family-based genetic study employing audiometric data. By using principal component analysis, we were able to reduce the dimensionality of this multivariate phenotype while capturing most of the variation and retaining biologically important features of the audiograms. We conducted a genome-wide association as well as a linkage scan with high-density SNP microarrays. Because of the presence of genetic population substructure, association testing was stratified after which evidence was combined by meta-analysis. No association signals reaching genome-wide significance were detected. Linkage analysis identified a linkage peak on 8q24.13-q24.22 for a trait correlated to audiogram shape. The signal reached genome-wide significance, as assessed by simulations. This finding represents the first locus for an ARHI trait.

AB - Age-related hearing impairment (ARHI), or presbycusis, is a very common multifactorial disorder. Despite the knowledge that genetics play an important role in the etiology of human ARHI as revealed by heritability studies, to date, its precise genetic determinants remain elusive. Here we report the results of a cross-sectional family-based genetic study employing audiometric data. By using principal component analysis, we were able to reduce the dimensionality of this multivariate phenotype while capturing most of the variation and retaining biologically important features of the audiograms. We conducted a genome-wide association as well as a linkage scan with high-density SNP microarrays. Because of the presence of genetic population substructure, association testing was stratified after which evidence was combined by meta-analysis. No association signals reaching genome-wide significance were detected. Linkage analysis identified a linkage peak on 8q24.13-q24.22 for a trait correlated to audiogram shape. The signal reached genome-wide significance, as assessed by simulations. This finding represents the first locus for an ARHI trait.

KW - Aged

KW - Aging/genetics

KW - Chromosomes, Human, Pair 8/genetics

KW - Cross-Sectional Studies

KW - Female

KW - Genetic Linkage

KW - Genome, Human

KW - Humans

KW - Male

KW - Middle Aged

KW - Polymorphism, Single Nucleotide

KW - Presbycusis/genetics

KW - Principal Component Analysis

KW - Quantitative Trait Loci

U2 - 10.1016/j.ajhg.2008.08.002

DO - 10.1016/j.ajhg.2008.08.002

M3 - Article

C2 - 18760390

VL - 83

SP - 401

EP - 407

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 3

ER -

Genome-wide SNP-based linkage scan identifies a locus on 8q24 for an age-related hearing impairment trait

Abstract

Keywords

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