| Title: | The genetic architecture of age-related hearing impairment revealed by genome-wide association analysis |
| Journal: | Communications Biology |
| Published: | 9 Jun 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/34108613/ |
| DOI: | https://doi.org/10.1038/s42003-021-02224-9 |
| URL: | https://www.nature.com/articles/s42003-021-02224-9.pdf |
Publication 9743
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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.</p>
28 Authors
- Erna V. Ivarsdottir
- Hilma Holm
- Stefania Benonisdottir
- Thorhildur Olafsdottir
- Gardar Sveinbjornsson
- Gudmar Thorleifsson
- Hannes P. Eggertsson
- Gisli H. Halldorsson
- Kristjan E. Hjorleifsson
- Pall Melsted
- Arnaldur Gylfason
- Gudny A. Arnadottir
- Asmundur Oddsson
- Brynjar O. Jensson
- Aslaug Jonasdottir
- Adalbjorg Jonasdottir
- Thorhildur Juliusdottir
- Lilja Stefansdottir
- Vinicius Tragante
- Bjarni V. Halldorsson
- Hannes Petersen
- Gudmundur Thorgeirsson
- Unnur Thorsteinsdottir
- Patrick Sulem
- Ingibjorg Hinriksdottir
- Ingileif Jonsdottir
- Daniel F. Gudbjartsson
- Kari Stefansson
1 Application
| Application ID | Title |
|---|---|
| 56270 | Evaluating and comparing sequence variant associations between the deCODE and UK Biobank datasets across a range of human traits |
Enabling scientific discoveries that improve human health