The genetic architecture of age-related hearing impairment revealed by genome-wide association analysis.

• Published in: Communications Biology
• Main Authors: Ivarsdottir, Erna V, Holm, Hilma, Benonisdottir, Stefania, Olafsdottir, Thorhildur, Sveinbjornsson, Gardar, Thorleifsson, Gudmar, Eggertsson, Hannes P, Halldorsson, Gisli H, Hjorleifsson, Kristjan E, Melsted, Pall, Gylfason, Arnaldur, Arnadottir, Gudny A, Oddsson, Asmundur, Jensson, Brynjar O, Jonasdottir, Aslaug, Jonasdottir, Adalbjorg, Juliusdottir, Thorhildur, Stefansdottir, Lilja, Tragante, Vinicius, Halldorsson, Bjarni V, Petersen, Hannes, Thorgeirsson, Gudmundur, Thorsteinsdottir, Unnur, Sulem, Patrick, Hinriksdottir, Ingibjorg, Jonsdottir, Ingileif, Gudbjartsson, Daniel F, Stefansson, Kari
• Other Authors: 1deCODE Genetics/Amgen, Reykjavik, Iceland. 2School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland. 3Department of Computing and Mathematical Sciences, California Institute of Technology, Pasadena, CA, USA. 4School of Technology, Reykjavik University, Reykjavik, Iceland. 5Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland. 6Akureyri Hospital, Akureyri, Iceland. 7Division of Cardiology, Department of Internal Medicine, Landspitali University Hospital, Reykjavik, Iceland. 8National Institute of Hearing and Speech in Iceland, Reykjavik, Iceland. 9Department of Immunology, Landspitali University Hospital, Reykjavik, Iceland. 10deCODE Genetics/Amgen, Reykjavik, Iceland. [e-mail]. 11School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland. [e-mail]. 12deCODE Genetics/Amgen, Reykjavik, Iceland. [e-mail]. 13Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland. [e-mail].
• Format: Article in Journal/Newspaper
• Language: English
• Published: Nature Publishing Group 2021
• Subjects: Heyrnarskerðing; Aldraðir; Gen; Hearing Loss; Aging; Genes; Iceland
• Online Access: http://hdl.handle.net/2336/621914; https://doi.org/10.1038/s42003-021-02224-9

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Download 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.