Disparities in discovery of pathogenic variants for autosomal recessive non-syndromic hearing impairment by ancestry

Eur J Hum Genet. 2019 Sep;27(9):1456-1465. doi: 10.1038/s41431-019-0417-2. Epub 2019 May 3.


Hearing impairment (HI) is characterized by extensive genetic heterogeneity. To determine the population-specific contribution of known autosomal recessive nonsyndromic (ARNS)HI genes and variants to HI etiology; pathogenic and likely pathogenic (PLP) ARNSHI variants were selected from ClinVar and the Deafness Variation Database and their frequencies were obtained from gnomAD for seven populations. ARNSHI prevalence due to PLP variants varies greatly by population ranging from 96.9 affected per 100,000 individuals for Ashkenazi Jews to 5.2 affected per 100,000 individuals for Africans/African Americans. For Europeans, Finns have the lowest prevalence due to ARNSHI PLP variants with 9.5 affected per 100,000 individuals. For East Asians, Latinos, non-Finish Europeans, and South Asians, ARNSHI prevalence due to PLP variants ranges from 17.1 to 33.7 affected per 100,000 individuals. ARNSHI variants that were previously reported in a single ancestry or family were observed in additional populations, e.g., USH1C p.(Q723*) reported in a Chinese family was the most prevalent pathogenic variant observed in gnomAD for African/African Americans. Variability between populations is due to how extensively ARNSHI has been studied, ARNSHI prevalence and ancestry specific ARNSHI variant architecture which is impacted by population history. Our study demonstrates that additional gene and variant discovery studies are necessary for all populations and particularly for individuals of African ancestry.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Chromosome Mapping
  • Deafness / diagnosis*
  • Deafness / genetics*
  • Gene Frequency
  • Genes, Recessive*
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Genetic Variation*
  • Hearing Loss / diagnosis*
  • Hearing Loss / genetics*
  • Humans

Supplementary concepts

  • Nonsyndromic Deafness