Benchek Penelope, Igo Robert P, Voss-Hoynes Heather, Wren Yvonne, Miller Gabrielle, Truitt Barbara, Zhang Wen, Osterman Michael, Freebairn Lisa, Tag Jessica, Taylor H Gerry, Chan E Ricky, Roussos Panos, Lewis Barbara, Stein Catherine M, Iyengar Sudha K
Department of Population & Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.
Bristol Dental School, Faculty of Health Sciences, University of Bristol, and Bristol Speech and Language Therapy Research Unit, North Bristol NHS Trust, Bristol, UK.
NPJ Genom Med. 2021 Jul 27;6(1):64. doi: 10.1038/s41525-021-00225-5.
Speech sound disorders (SSD) manifest as difficulties in phonological memory and awareness, oral motor function, language, vocabulary, reading, and spelling. Families enriched for SSD are rare, and typically display a cluster of deficits. We conducted a genome-wide association study (GWAS) in 435 children from 148 families in the Cleveland Family Speech and Reading study (CFSRS), examining 16 variables representing 6 domains. Replication was conducted using the Avon Longitudinal Study of Parents and Children (ALSPAC). We identified 18 significant loci (combined p < 10) that we pursued bioinformatically. We prioritized 5 novel gene regions with likely functional repercussions on neural pathways, including those which colocalized with differentially methylated regions in our sample. Polygenic risk scores for receptive language, expressive vocabulary, phonological awareness, phonological memory, spelling, and reading decoding associated with increasing clinical severity. In summary, neural-genetic influence on SSD is primarily multigenic and acts on genomic regulatory elements, similar to other neurodevelopmental disorders.
语音障碍（SSD）表现为语音记忆与意识、口腔运动功能、语言、词汇、阅读和拼写方面的困难。SSD患者富集的家庭较为罕见，且通常表现出一系列缺陷。我们在克利夫兰家庭语音与阅读研究（CFSRS）中，对148个家庭的435名儿童进行了全基因组关联研究（GWAS），研究了代表6个领域的16个变量。使用阿冯亲子纵向研究（ALSPAC）进行了重复验证。我们确定了18个显著位点（合并p<10），并对其进行了生物信息学追踪。我们优先考虑了5个对神经通路可能具有功能影响的新基因区域，包括那些与我们样本中差异甲基化区域共定位的区域。接受性语言、表达性词汇、语音意识、语音记忆、拼写和阅读解码的多基因风险评分与临床严重程度增加相关。总之，与其他神经发育障碍类似，对SSD的神经遗传影响主要是多基因的，并作用于基因组调控元件。
