Original article 137 Further evidence for a susceptibility locus contributing to reading disability on chromosome 15q15–q21 Johannes Schumacher a , Inke R. Ko ¨ nig c , Tatjana Schro ¨ der a , Maike Duell a , Ellen Plume d , Peter Propping a , Andreas Warnke d , Claudia Libertus e , Andreas Ziegler c , Bertram Mu ¨ ller-Myhsok f , Gerd Schulte-Ko ¨ rne g and Markus M. No ¨ then b Background Linkage and association studies in dyslexia suggest that a susceptibility locus exists on chromosome 15q15–q21. Objective This study aims to evaluate these findings in an independent sample of dyslexia. Methods We performed linkage and association analyses using 82 families with dyslexia and 19 STR markers covering the target region on chromosome 15q. Results We observed suggestive evidence for linkage at STR-marker D15S143; this was the strongest implicated marker in the previous linkage studies on dyslexia. At the association level, linkage disequilibrium (LD) was found between dyslexia and markers within a circumscribed genomic region recently implicated in two independent studies on dyslexia. Conclusion Our data and the previous reported findings present convincing evidence for a dyslexia-related gene within the identified linkage and LD region on chromosome 15q. However, at this stage it seems difficult to determine whether the linkage and association findings point to more than one susceptibility loci within this region. A definite answer to this question will require systematic single nucleotide polymorphism-based LD mapping within the implicated region, which should lead to the identification of the true dyslexia susceptibility gene(s). Psychiatr Genet 18:137–142  c 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins. Psychiatric Genetics 2008, 18:137–142 Keywords: association, chromosome 15, dyslexia, DYX1, linkage a Institute of Human Genetics, University of Bonn, b Department of Genomics, Life and Brain Centre, University of Bonn, Bonn, c Institute of Medical Biometry and Statistics, University Hospital Schleswig-Holstein-Campus Lu ¨ beck, Lu ¨ beck, d Department of Child and Adolescent Psychiatry and Psychotherapy, University of Wu ¨ rzburg, Wu ¨ rzburg, e Department of Child and Adolescent Psychiatry and Psychotherapy, University of Marburg, Marburg, f Max-Planck Institute of Psychiatry and g Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Ludwig-Maximilians-University of Munich, Munich, Germany Correspondence to Dr Markus M. No ¨ then, Department of Genomics, Life and Brain Centre, University of Bonn, Sigmund-Freud-Street 25, Bonn D-53127, Germany Tel: + 49 228 287 22644; e-mail: markus.noethen@uni-bonn.de Received 12 January 2007 Revised 18 September 2007 Accepted 26 September 2007 Introduction Dyslexia (MIM 6002002) is the most frequently diag- nosed learning disorder (Lerner, 1989; Schulte-Ko ¨rne, 2001); affecting 5–12% of school-age children and is associated with major educational, social, and emotional repercussions (Shaywitz et al., 1990; Katusic et al., 2001). The familial nature of dyslexia was recognized when the disorder was first described and has since become well established (Hinshelwood, 1895; Stephenson, 1907; Fisher and DeFries, 2002). Twin studieshave shown that the tendency for familial clustering is primarily because of genetic factors rather than shared environment, with heritability estimates ranging up to 0.70 for spelling and 0.50 for reading (DeFries et al., 1987; Stevenson et al., 1987; Olson and Wise, 1994; Gayan and Olson, 2001; Plomin and Kovas, 2005). The core phenotype of dyslexia is characterized by a lower spelling ability, a lower word reading accuracy, and fluency (Dilling et al., 1991). Several cognitive abilities have been found to be correlated with the core symptoms (Gayan and Olson, 2001) and these might characterize dyslexia subtypes (Bates et al., 2007a). These are phonological decoding, phoneme awareness, orthographic processing, and rapid naming (Schulte- Ko ¨rne et al., 2007). Genetically, it is likely that multiple genes of small-to-moderate effect are involved in the disease process, with some contributing to general and others to specific phenotypic deficits (Lewitter et al., 1980; Lewis et al., 1993; Wijsman et al., 2000; Schulte- Ko ¨rne, 2001; Chapman et al., 2003). Despite the most recent and promising association findings within a dyslexia linkage region on 6p22 (Deffenbacher et al., 2004; Francks et al., 2004; Cope et al., 2005; Meng et al., 2005; Schumacher et al., 2006a), nine other chromosomal regions likely to contain dyslexia genes were suggested through replicated linkage studies and have been listed by the Human Gene Nomenclature Committee (reviewed by Schumacher et al., 2007). Of 0955-8829  c 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.