A Large Genome-Wide Association Study of Age-Related Hearing Impairment Using Electronic Health Records.
Age-related hearing impairment (ARHI), one of the most common sensory disorders, can be mitigated, but not cured or eliminated. To identify genetic influences underlying ARHI, we conducted a genome-wide association study of ARHI in 6,527 cases and 45,882 controls among the non-Hispanic whites from t...
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Public Library of Science (PLoS)
2016-10-01
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| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1006371&type=printable |
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| author | Thomas J Hoffmann Bronya J Keats Noriko Yoshikawa Catherine Schaefer Neil Risch Lawrence R Lustig |
| author_facet | Thomas J Hoffmann Bronya J Keats Noriko Yoshikawa Catherine Schaefer Neil Risch Lawrence R Lustig |
| author_sort | Thomas J Hoffmann |
| collection | DOAJ |
| description | Age-related hearing impairment (ARHI), one of the most common sensory disorders, can be mitigated, but not cured or eliminated. To identify genetic influences underlying ARHI, we conducted a genome-wide association study of ARHI in 6,527 cases and 45,882 controls among the non-Hispanic whites from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. We identified two novel genome-wide significant SNPs: rs4932196 (odds ratio = 1.185, p = 4.0x10-11), 52Kb 3' of ISG20, which replicated in a meta-analysis of the other GERA race/ethnicity groups (1,025 cases, 12,388 controls, p = 0.00094) and in a UK Biobank case-control analysis (30,802 self-reported cases, 78,586 controls, p = 0.015); and rs58389158 (odds ratio = 1.132, p = 1.8x10-9), which replicated in the UK Biobank (p = 0.00021). The latter SNP lies just outside exon 8 and is highly correlated (r2 = 0.96) with the missense SNP rs5756795 in exon 7 of TRIOBP, a gene previously associated with prelingual nonsyndromic hearing loss. We further tested these SNPs in phenotypes from audiologist notes available on a subset of GERA (4,903 individuals), stratified by case/control status, to construct an independent replication test, and found a significant effect of rs58389158 on speech reception threshold (SRT; overall GERA meta-analysis p = 1.9x10-6). We also tested variants within exons of 132 other previously-identified hearing loss genes, and identified two common additional significant SNPs: rs2877561 (synonymous change in ILDR1, p = 6.2x10-5), which replicated in the UK Biobank (p = 0.00057), and had a significant GERA SRT (p = 0.00019) and speech discrimination score (SDS; p = 0.0019); and rs9493627 (missense change in EYA4, p = 0.00011) which replicated in the UK Biobank (p = 0.0095), other GERA groups (p = 0.0080), and had a consistent significant result for SRT (p = 0.041) and suggestive result for SDS (p = 0.081). Large cohorts with GWAS data and electronic health records may be a useful method to characterize the genetic architecture of ARHI. |
| format | Article |
| id | doaj-art-ccbfdb98c98e4eb6aa0f82aac1029c78 |
| institution | Kabale University |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2016-10-01 |
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| spelling | doaj-art-ccbfdb98c98e4eb6aa0f82aac1029c782025-08-20T03:24:29ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042016-10-011210e100637110.1371/journal.pgen.1006371A Large Genome-Wide Association Study of Age-Related Hearing Impairment Using Electronic Health Records.Thomas J HoffmannBronya J KeatsNoriko YoshikawaCatherine SchaeferNeil RischLawrence R LustigAge-related hearing impairment (ARHI), one of the most common sensory disorders, can be mitigated, but not cured or eliminated. To identify genetic influences underlying ARHI, we conducted a genome-wide association study of ARHI in 6,527 cases and 45,882 controls among the non-Hispanic whites from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. We identified two novel genome-wide significant SNPs: rs4932196 (odds ratio = 1.185, p = 4.0x10-11), 52Kb 3' of ISG20, which replicated in a meta-analysis of the other GERA race/ethnicity groups (1,025 cases, 12,388 controls, p = 0.00094) and in a UK Biobank case-control analysis (30,802 self-reported cases, 78,586 controls, p = 0.015); and rs58389158 (odds ratio = 1.132, p = 1.8x10-9), which replicated in the UK Biobank (p = 0.00021). The latter SNP lies just outside exon 8 and is highly correlated (r2 = 0.96) with the missense SNP rs5756795 in exon 7 of TRIOBP, a gene previously associated with prelingual nonsyndromic hearing loss. We further tested these SNPs in phenotypes from audiologist notes available on a subset of GERA (4,903 individuals), stratified by case/control status, to construct an independent replication test, and found a significant effect of rs58389158 on speech reception threshold (SRT; overall GERA meta-analysis p = 1.9x10-6). We also tested variants within exons of 132 other previously-identified hearing loss genes, and identified two common additional significant SNPs: rs2877561 (synonymous change in ILDR1, p = 6.2x10-5), which replicated in the UK Biobank (p = 0.00057), and had a significant GERA SRT (p = 0.00019) and speech discrimination score (SDS; p = 0.0019); and rs9493627 (missense change in EYA4, p = 0.00011) which replicated in the UK Biobank (p = 0.0095), other GERA groups (p = 0.0080), and had a consistent significant result for SRT (p = 0.041) and suggestive result for SDS (p = 0.081). Large cohorts with GWAS data and electronic health records may be a useful method to characterize the genetic architecture of ARHI.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1006371&type=printable |
| spellingShingle | Thomas J Hoffmann Bronya J Keats Noriko Yoshikawa Catherine Schaefer Neil Risch Lawrence R Lustig A Large Genome-Wide Association Study of Age-Related Hearing Impairment Using Electronic Health Records. PLoS Genetics |
| title | A Large Genome-Wide Association Study of Age-Related Hearing Impairment Using Electronic Health Records. |
| title_full | A Large Genome-Wide Association Study of Age-Related Hearing Impairment Using Electronic Health Records. |
| title_fullStr | A Large Genome-Wide Association Study of Age-Related Hearing Impairment Using Electronic Health Records. |
| title_full_unstemmed | A Large Genome-Wide Association Study of Age-Related Hearing Impairment Using Electronic Health Records. |
| title_short | A Large Genome-Wide Association Study of Age-Related Hearing Impairment Using Electronic Health Records. |
| title_sort | large genome wide association study of age related hearing impairment using electronic health records |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1006371&type=printable |
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