title: Polymorphisms in DCDC2 and S100B associate with developmental dyslexia.
abstract: Genetic studies of complex traits have become increasingly successful as progress is made in next-generation sequencing. We aimed at discovering single nucleotide variation present in known and new candidate genes for developmental dyslexia: CYP19A1, DCDC2, DIP2A, DYX1C1, GCFC2 (also known as C2orf3), KIAA0319, MRPL19, PCNT, PRMT2, ROBO1 and S100B. We used next-generation sequencing to identify single-nucleotide polymorphisms in the exons of these 11 genes in pools of 100 DNA samples of Finnish individuals with developmental dyslexia. Subsequent individual genotyping of those 100 individuals, and additional cases and controls from the Finnish and German populations, validated 92 out of 111 different single-nucleotide variants. A nonsynonymous polymorphism in DCDC2 (corrected P = 0.002) and a noncoding variant in S100B (corrected P = 0.016) showed a significant association with spelling performance in families of German origin. No significant association was found for the variants neither in the Finnish case-control sample set nor in the Finnish family sample set. Our findings further strengthen the role of DCDC2 and implicate S100B, in the biology of reading and spelling.
authors: Department of Biosciences and Nutrition, and Center for Innovative Medicine, Karolinska Institutet, Huddinge, Sweden.
authors: Hans
authors: H
authors: Matsson
authors: 1] Science for Life Laboratory, Stockholm, Sweden [2] Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
authors: Mikael
authors: M
authors: Huss
authors: Department of Biosciences and Nutrition, and Center for Innovative Medicine, Karolinska Institutet, Huddinge, Sweden.
authors: Helena
authors: H
authors: Persson
authors: Department of Biosciences and Nutrition, and Center for Innovative Medicine, Karolinska Institutet, Huddinge, Sweden.
authors: Elisabet
authors: E
authors: Einarsdottir
authors: Department of Biosciences and Nutrition, and Center for Innovative Medicine, Karolinska Institutet, Huddinge, Sweden.
authors: Ettore
authors: E
authors: Tiraboschi
authors: Division of Child Neurology, Department of Gynecology and Pediatrics, Jorvi Hospital, University Central Hospital, Espoo, Finland.
authors: Jaana
authors: J
authors: Nopola-Hemmi
authors: Institute of Human Genetics and Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
authors: Johannes
authors: J
authors: Schumacher
authors: Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Munich, Munich, Germany.
authors: Nina
authors: N
authors: Neuhoff
authors: Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany.
authors: Andreas
authors: A
authors: Warnke
authors: Department of Psychology and Child Research Center, University of Jyväskylä, Jyväskylä, Finland.
authors: Heikki
authors: H
authors: Lyytinen
authors: Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Munich, Munich, Germany.
authors: Gert
authors: G
authors: Schulte-Körne
authors: Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
authors: Markus M
authors: MM
authors: Nöthen
authors: Department of Psychology, University of Jyväskylä, Jyväskylä, Finland.
authors: Paavo H T
authors: PH
authors: Leppänen
authors: Department of Biosciences and Nutrition, and Center for Innovative Medicine, Karolinska Institutet, Huddinge, Sweden.
authors: Myriam
authors: M
authors: Peyrard-Janvid
authors: 1] Department of Biosciences and Nutrition, and Center for Innovative Medicine, Karolinska Institutet, Huddinge, Sweden [2] Science for Life Laboratory, Stockholm, Sweden [3] Molecular Neurology Research Program, Research Programs Unit, University of Helsinki, Helsinki, Finland [4] Folkhälsan Institute of Genetics, Helsinki, Finland.
authors: Juha
authors: J
authors: Kere
mesh_terms: D016022:Case-Control Studies; D004410:Dyslexia / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D064568:S100 Calcium Binding Protein beta Subunit / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: C510451:DCDC2 protein, human; D008869:Microtubule-Associated Proteins; D064568:S100 Calcium Binding Protein beta Subunit; C579160:S100B protein, human