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A Large Genome-Wide Association Study of Age-Related Hearing Impairment Using Electronic Health Records.

ABSTRACT: 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.

SUBMITTER: Hoffmann TJ

PROVIDER: S-EPMC5072625 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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A Large Genome-Wide Association Study of Age-Related Hearing Impairment Using Electronic Health Records.

Hoffmann Thomas J TJ Keats Bronya J BJ Yoshikawa Noriko N Schaefer Catherine C Risch Neil N Lustig Lawrence R LR

PLoS genetics 20161020 10

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 r ...[more]

PMID: 27764096

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Project description:Introduction: Despite growing recognition of hearing loss as a risk factor for late life cognitive disorders, sex and gender analysis of this association has been limited. Elucidating this is one means to advocate for holistic medicine by considering the psychosocial attributes of people. With a composite Gender Score (GS), we aimed to assess this among aging participants (50+) from the 2016 Health and Retirement Study (HRS) cohort. Methods: The GS was derived from gender-related variables in HRS by factor analyses and logistic regression, ranging from 0 (toward masculinity) to 100 (toward femininity). GS tertiles were also used to indicate three gender types (GS tertile 1: lower GS indicates masculinity; GS tertile 2: middle GS indicates androgyny; GS tertile 3: higher GS indicates femininity). Univariate followed by multiple logistic regressions were used to estimate the Odds Ratio (OR) and 95% confidence intervals (CI) of cognitive impairment (assessed by adapted Telephone Interview for Cognitive Status) from hearing acuity, as well as to explore the interactions of sex and gender with hearing acuity. The risk of cognitive impairment among hearing-impaired participants was assessed using multivariable models including sex and gender as exposure variables. Results: Five variables (taking risks, loneliness, housework, drinking, and depression) were retained to compute the GS for each participant. The distribution of GS between sexes partly overlapped. After adjusting for confounding factors, the OR for cognitive impairment associated with hearing impairment was significantly higher (OR = 1.65, 95% CI: 1.26, 2.15), and this association was not modified by female sex (OR = 0.77, 95% CI: 0.46, 1.27), but by androgynous gender (OR = 0.44, 95% CI: 0.24, 0.81). In the multivariable models for participants with hearing impairment, androgynous and feminine gender, as opposed to female sex, was associated with lower odds of cognitive impairment (OR of GS tertile 2 = 0.59, 95% CI: 0.41, 0.84; OR of GS tertile 3 = 0.60, 95% CI: 0.41, 0.87; OR of female sex = 0.78, 95% CI: 0.57, 1.08). Conclusions: Hearing impairment was associated with cognitive impairment among older people, and this association may be attenuated by a more feminine GS.

Project description:Importance:Evidence has linked age-related hearing impairment (ARHI) with cognitive decline; however, very few studies (none in the United Kingdom) explore this link in large well-characterized groups of community-dwelling individuals. Objective:To investigate the link between ARHI and cognitive decline using a cohort of elderly individuals from the United Kingdom and explore untreated hearing loss and social isolation as potential explanations for the observed link. Design, Setting, and Participants:This cross-sectional analysis of wave 7 (June 2014 through May 2015) of the English Longitudinal Study of Ageing (ELSA) sampled men and women 50 years or older and living in the United Kingdom in a community setting. Those with a diagnosis of dementia, Alzheimer disease, or Parkinson disease or with ear infections and cochlear implants were excluded. Data were analyzed from August 1, 2017, through May 25, 2018. Main Outcomes and Measures:Memory and executive function as measures of cognitive function and hearing acuity derived from the HearCheck screener device (Siemens). Results:Of a cohort of 9666 members in wave 7 of ELSA, 7385 were eligible for analysis after applying exclusion criteria (55.1% women; mean [SD] age, 67.4 [9.4] years). Of these, 3056 (41.4%) had mild hearing loss and 755 (10.2%) had severe hearing loss; 834 (11.3%) used a hearing aid; and 7155 (96.9%) were white. Hearing loss had a negative association with cognition; for those with moderate to severe loss, the score on memory assessment was a full 1 point less (-1.00; 95% CI, -1.24 to -0.76), ceteris paribus, relative to those with no hearing loss. However, this association was seen only in the individuals with untreated hearing loss (ie, those who did not use hearing aids) (-1.16; 95% CI, -1.45 to -0.87). Evidence suggests that social isolation acts as a mediating factor. Conclusions and Relevance:Although hearing loss and cognition are linked, untreated hearing loss drives the association. Social isolation is a mediating factor in the link for those who have untreated hearing loss. Cognitive decline associated with ARHI is probably preventable by early rehabilitation and increased opportunistic screening for the elderly.

Dataset Information

A Large Genome-Wide Association Study of Age-Related Hearing Impairment Using Electronic Health Records.

Publications

A Large Genome-Wide Association Study of Age-Related Hearing Impairment Using Electronic Health Records.

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