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Communication disorders, including speech sound disorder (<jats:styled-content style=\"fixed-case\">SSD<\/jats:styled-content>), can impair a child's academic, social and behavioral development. Speech sound disorder is a complex, polygenic trait with a substantial genetic component. However, specific genes that contribute to <jats:styled-content style=\"fixed-case\">SSD<\/jats:styled-content> remain largely unknown. To identify associated genes, we assessed the association of the <jats:styled-content style=\"fixed-case\">DYX2<\/jats:styled-content> dyslexia risk locus and markers in neurochemical signaling genes (e.g., nicotinic and dopaminergic) with <jats:styled-content style=\"fixed-case\">SSD<\/jats:styled-content> and related endophenotypes. We first performed separate primary associations in two independent samples\u00a0\u2013\u00a0Cleveland <jats:styled-content style=\"fixed-case\">SSD<\/jats:styled-content> (210 affected and 257 unaffected individuals in 127 families) and Denver <jats:styled-content style=\"fixed-case\">SSD<\/jats:styled-content> (113 affected individuals and 106 unaffected individuals in 85 families)\u00a0\u2013\u00a0and then combined results by meta\u2010analysis. <jats:styled-content style=\"fixed-case\">DYX2<\/jats:styled-content> markers, specifically those in the 3\u2032 untranslated region of <jats:italic><jats:styled-content style=\"fixed-case\">DCDC2<\/jats:styled-content><\/jats:italic> (<jats:italic>P<\/jats:italic> = 1.43 \u00d7 10<jats:sup>\u22124<\/jats:sup>), showed the strongest associations with phonological awareness. We also observed suggestive associations of dopaminergic\u2010related genes <jats:italic><jats:styled-content style=\"fixed-case\">ANKK1<\/jats:styled-content><\/jats:italic> (<jats:italic>P<\/jats:italic> = 1.02 \u00d7 10<jats:sup>\u22122<\/jats:sup>) and <jats:italic><jats:styled-content style=\"fixed-case\">DRD2<\/jats:styled-content><\/jats:italic> (<jats:italic>P<\/jats:italic> = 9.22 \u00d7 10<jats:sup>\u22123<\/jats:sup>) and nicotinic\u2010related genes <jats:italic><jats:styled-content style=\"fixed-case\">CHRNA3<\/jats:styled-content><\/jats:italic> (<jats:italic>P<\/jats:italic> = 2.51 \u00d7 10<jats:sup>\u22123<\/jats:sup>) and <jats:italic><jats:styled-content style=\"fixed-case\">BDNF<\/jats:styled-content><\/jats:italic> (<jats:italic>P<\/jats:italic> = 8.14 \u00d7 10<jats:sup>\u22123<\/jats:sup>) with case\u2013control status and articulation. Our results further implicate variation in putative regulatory regions in the <jats:styled-content style=\"fixed-case\">DYX2<\/jats:styled-content> locus, particularly in <jats:italic><jats:styled-content style=\"fixed-case\">DCDC2<\/jats:styled-content><\/jats:italic>, influencing language and cognitive traits. The results also support previous studies implicating variation in dopaminergic and nicotinic neural signaling influencing human communication and cognitive development. Our findings expand the literature showing genetic factors (e.g., <jats:styled-content style=\"fixed-case\">DYX2<\/jats:styled-content>) contributing to multiple related, yet distinct neurocognitive domains (e.g., dyslexia, language impairment, and <jats:styled-content style=\"fixed-case\">SSD<\/jats:styled-content>). How these factors interactively yield different neurocognitive and language\u2010related outcomes remains to be elucidated.<\/jats:p>","DOI":"10.1111\/gbb.12214","type":"journal-article","created":{"date-parts":[[2015,3,16]],"date-time":"2015-03-16T08:18:56Z","timestamp":1426493936000},"page":"377-385","source":"Crossref","is-referenced-by-count":8,"title":["The <scp>DYX2<\/scp> locus and neurochemical signaling genes contribute to speech sound disorder and related neurocognitive domains"],"prefix":"10.1111","volume":"14","author":[{"given":"J. D.","family":"Eicher","sequence":"first","affiliation":[{"name":"Department of Genetics Yale University School of Medicine  New Haven CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. M.","family":"Stein","sequence":"additional","affiliation":[{"name":"Department of Epidemiology &amp; Biostatistics Case Western Reserve University  Cleveland OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Epidemiology &amp; Biostatistics Case Western Reserve University  Cleveland OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. A.","family":"Ciesla","sequence":"additional","affiliation":[{"name":"Department of Epidemiology &amp; Biostatistics Case Western Reserve University  Cleveland OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. R.","family":"Powers","sequence":"additional","affiliation":[{"name":"Department of Genetics Yale University School of Medicine  New Haven CT"},{"name":"Department of Pediatrics Yale University School of Medicine  New Haven CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Boada","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Colorado School of Medicine  Aurora CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. D.","family":"Smith","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Developmental Neuroscience University of Nebraska Medical Center  Omaha NE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. F.","family":"Pennington","sequence":"additional","affiliation":[{"name":"Department of Psychology University of Denver  Denver CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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