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Association between AVPR1A, DRD2, and ASPM and endophenotypes of communication disorders

Stein, Catherine M.a,e; Truitt, Barbaraa; Deng, Fenghuaa; Ciesla, Allison Avricha; Qiu, Feiyoua; Joseph, Peronnea; Raghavendra, Rekhaa; Fondran, Jeremya; Igo, Robert P. Jra; Tag, Jessicab; Freebairn, Lisab; Taylor, H. Gerryb,c; Lewis, Barbara A.b; Iyengar, Sudha K.a,d

doi: 10.1097/YPG.0000000000000045
Original Articles

Objectives Speech sound disorder (SSD) is one of the most common communication disorders, with a prevalence rate of 16% at 3 years of age, and an estimated 3.8% of children still presenting speech difficulties at 6 years of age. Several studies have identified promising associations between communication disorders and genes in brain and neuronal pathways; however, there have been few studies focusing on SSD and its associated endophenotypes. On the basis of the hypothesis that neuronal genes may influence endophenotypes common to communication disorders, we focused on three genes related to brain and central nervous system functioning: the dopamine D2 receptor (DRD2) gene, the arginine–vasopressin receptor 1a (AVPR1A) gene, and the microcephaly-associated protein gene (ASPM).

Methods We examined the association of these genes with key endophenotypes of SSD – phonological memory measured through multisyllabic and nonword repetition, vocabulary measured using the Expressive One Word Picture Vocabulary Test and Peabody Picture Vocabulary Test, and reading decoding measured using the Woodcock Reading Mastery Tests Revised – as well as with the clinical phenotype of SSD. We genotyped tag single nucleotide polymorphisms in these genes and examined 498 individuals from 180 families.

Results These data show that several single nucleotide polymorphisms in all three genes were associated with phonological memory, vocabulary, and reading decoding, with P less than 0.05. Notably, associations in AVPR1A (rs11832266) were significant after multiple testing correction. Gene-level tests showed that DRD2 was associated with vocabulary, ASPM with vocabulary and reading decoding, and AVPR1A with all three endophenotypes.

Conclusion Endophenotypes common to SSD, language impairment, and reading disability are all associated with these neuronal pathway genes.

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Departments of aEpidemiology and Biostatistics

bPsychological Sciences



eCenter for Proteomics and Bioinformatics, Case Western Reserve University, Cleveland, Ohio, USA

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Correspondence to Catherine M. Stein, PhD, Department of Epidemiology and Biostatistics, Case Western Reserve University, 2103 Cornell Rd, Wolstein Research Building, Cleveland, OH 44106, USA Tel: +1 216 368 5631; fax: +1 216 368 4880; e-mail:

Received August 8, 2013

Accepted April 20, 2014

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins