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The genetic architecture of age-related hearing impairment revealed by genome-wide association analysis
- Source :
- Communications Biology, Vol 4, Iss 1, Pp 1-13 (2021), Communications Biology
- Publication Year :
- 2021
- Publisher :
- Nature Portfolio, 2021.
-
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.<br />Erna Ivarsdottir et al. report a genome-wide association meta-analysis for age-related hearing loss in the Icelandic and UK populations. They identify 21 novel variants, 13 of which are rare, and reveal a genetic correlation between age-related hearing loss and tinnitus.
- Subjects :
- 0301 basic medicine
Adult
Male
Aging
Hearing loss
QH301-705.5
Medicine (miscellaneous)
Genome-wide association study
Biology
Genetic correlation
Genome-wide association studies
General Biochemistry, Genetics and Molecular Biology
Article
03 medical and health sciences
symbols.namesake
0302 clinical medicine
Risk Factors
medicine
otorhinolaryngologic diseases
Missense mutation
Humans
Genetic Predisposition to Disease
Biology (General)
Hearing Loss
Aged
Genetic association study
Genetics
Aged, 80 and over
Genetic Variation
Middle Aged
Genetic architecture
Ageing
030104 developmental biology
Genes
Mendelian inheritance
symbols
Female
Tandem exon duplication
medicine.symptom
General Agricultural and Biological Sciences
030217 neurology & neurosurgery
Tinnitus
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- ISSN :
- 23993642
- Volume :
- 4
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Communications Biology
- Accession number :
- edsair.doi.dedup.....6fb79b19eb362d96c54b612004daf786