Disparities in discovery of pathogenic variants for autosomal recessive non-syndromic hearing impairment by ancestry
Disparities in discovery of pathogenic variants for autosomal recessive non-syndromic hearing impairment by ancestry
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DOI：
10.1038/s41431-019-0417-2
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发表时间：
2019-09-01
影响因子：
5.2
通讯作者：
Leal, Suzanne M.
中科院分区：
文献类型：
--
作者：
Chakchouk, Imen;Zhang, Di;Leal, Suzanne M.
听力障碍（hearing impairment，HI）的特征是广泛的遗传异质性。为了确定已知的常染色体隐性遗传非综合征（ARNS）HI基因和变体对HI病因的人群特异性贡献;从ClinVar和耳聋变异数据库中选择致病性和可能致病性（PLP）ARNSHI变体，并从gnomAD中获得7个人群的频率。PLP变异导致的ARNSHI患病率因人群而异，从德系犹太人的每10万人中有96.9人受影响到非洲人/非裔美国人的每10万人中有5.2人受影响。对于欧洲人来说，芬兰人由于ARNSHI PLP变异而患病率最低，每10万人中有9.5人受影响。对于东亚人，拉丁美洲人，非芬兰欧洲人和南亚人，由于PLP变异导致的ARNSHI患病率范围为每10万人17.1至33.7人。先前在单一祖先或家族中报告的ARNSHI变体在其他人群中观察到，USH1C p. (Q723* ）是在非裔/非裔美国人的gnomAD中观察到的最常见的致病性变体。人群之间的变异性是由于ARNSHI研究的广泛程度、ARNSHI患病率和受人群历史影响的祖先特异性ARNSHI变体结构。我们的研究表明，额外的基因和变异发现研究是必要的所有人群，特别是非洲血统的个人。
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.