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

Erna V IvarsdottirHilma HólmStefania BenonisdottirThorhildur OlafsdottirGardar SveinbjornssonGudmar ThorleifssonHannes P EggertssonGisli Hreinn HalldorssonKristján Eldjárn HjörleifssonPall MelstedArnaldur GylfasonGudny Anna ArnadottirAsmundur OddssonBrynjar O JenssonAslaug JonasdottirAdalbjorg JonasdottirThorhildur JuliusdottirLilja StefansdottirVinicius TraganteBjarni V HalldórssonHannes PetersenGudmundur ThorgeirssonUnnur ThorsteinsdottirPatrick SulemIngibjorg HinriksdottirIngileif JónsdóttirDaníel F GuðbjartssonKari Stefansson
Published in: Communications biology (2021)
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.
Keyphrases
  • copy number
  • genome wide
  • genome wide association
  • hearing loss
  • dna methylation
  • wastewater treatment
  • gene expression
  • cross sectional