Strong genetic evidence of DCDC2 as a susceptibility gene for dyslexia

Johannes Schumacher; Heidi Anthoni; Faten Dahdouh; Inke R. König; Axel M. Hillmer; Nadine Kluck; Malou Manthey; Ellen Plume; Andreas Warnke; Helmut Remschmidt; Jutta Hülsmann; Sven Cichon; Cecilia M. Lindgren; Peter Propping; Marco Zucchelli; Andreas Ziegler; Myriam Peyrard-Janvid; Gerd Schulte-Körne; Markus M. Nöthen; Juha Kere

doi:10.1086/498992

Strong genetic evidence of DCDC2 as a susceptibility gene for dyslexia

Johannes Schumacher^*, Heidi Anthoni, Faten Dahdouh, Inke R. König, Axel M. Hillmer, Nadine Kluck, Malou Manthey, Ellen Plume, Andreas Warnke, Helmut Remschmidt, Jutta Hülsmann, Sven Cichon, Cecilia M. Lindgren, Peter Propping, Marco Zucchelli, Andreas Ziegler, Myriam Peyrard-Janvid, Gerd Schulte-Körne, Markus M. Nöthen, Juha Kere

^*Korrespondierende/r Autor/-in für diese Arbeit

Institut für Medizinische Biometrie und Statistik

218 Zitate (Scopus)

Abstract

We searched for linkage disequilibrium (LD) in 137 triads with dyslexia, using markers that span the most-replicated dyslexia susceptibility region on 6p21-p22, and found association between the disease and markers within the VMP/DCDC2/KAAG1 locus. Detailed refinement of the LD region, involving sequencing and genotyping of additional markers, showed significant association within DCDC2 in single-marker and haplotype analyses. The association appeared to be strongest in severely affected patients. In a second step, the study was extended to include an independent sample of 239 triads with dyslexia, in which the association-in particular, with the severe phenotype of dyslexia-was confirmed. Our expression data showed that DCDC2, which contains a doublecortin homology domain that is possibly involved in cortical neuron migration, is expressed in the fetal and adult CNS, which-together with the hypothesized protein function-is in accordance with findings in dyslexic patients with abnormal neuronal migration and maturation.

Originalsprache	Englisch
Zeitschrift	American Journal of Human Genetics
Jahrgang	78
Ausgabenummer	1
Seiten (von - bis)	52-62
Seitenumfang	11
ISSN	0002-9297
DOIs	https://doi.org/10.1086/498992
Publikationsstatus	Veröffentlicht - 01.2006

Fördermittel

We are grateful to all investigated individuals for their cooperation in this study. This study was supported by the Deutsche Forschungsgemeinschaft. P.P. was supported by the National Genomic Network of the Bundesministerium für Bildung und Forschung. M.M.N. received support for this work from the Alfried Krupp von Bohlen und Halbach-Stiftung. M.P.-J. is a recipient of a research position from the Swedish Research Council (Vetenskpsrådet). J.K. is supported by grants from the Swedish Research Council, the Academy of Finland, the Sigrid Jusélius Foundation, and the Päivikki and Sakari Sohlberg Foundation. Some of the results were obtained by using the program package S.A.G.E., which is supported by U.S. Public Health Service Resource grant RR03655 from the National Center for Research Resources.

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10.1086/498992

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Schumacher, J., Anthoni, H., Dahdouh, F., König, I. R., Hillmer, A. M., Kluck, N., Manthey, M., Plume, E., Warnke, A., Remschmidt, H., Hülsmann, J., Cichon, S., Lindgren, C. M., Propping, P., Zucchelli, M., Ziegler, A., Peyrard-Janvid, M., Schulte-Körne, G., Nöthen, M. M., & Kere, J. (2006). Strong genetic evidence of DCDC2 as a susceptibility gene for dyslexia. American Journal of Human Genetics, 78(1), 52-62. https://doi.org/10.1086/498992

@article{239be33d1b724500b710095246777cfb,

title = "Strong genetic evidence of DCDC2 as a susceptibility gene for dyslexia",

abstract = "We searched for linkage disequilibrium (LD) in 137 triads with dyslexia, using markers that span the most-replicated dyslexia susceptibility region on 6p21-p22, and found association between the disease and markers within the VMP/DCDC2/KAAG1 locus. Detailed refinement of the LD region, involving sequencing and genotyping of additional markers, showed significant association within DCDC2 in single-marker and haplotype analyses. The association appeared to be strongest in severely affected patients. In a second step, the study was extended to include an independent sample of 239 triads with dyslexia, in which the association-in particular, with the severe phenotype of dyslexia-was confirmed. Our expression data showed that DCDC2, which contains a doublecortin homology domain that is possibly involved in cortical neuron migration, is expressed in the fetal and adult CNS, which-together with the hypothesized protein function-is in accordance with findings in dyslexic patients with abnormal neuronal migration and maturation.",

author = "Johannes Schumacher and Heidi Anthoni and Faten Dahdouh and K{\"o}nig, \{Inke R.\} and Hillmer, \{Axel M.\} and Nadine Kluck and Malou Manthey and Ellen Plume and Andreas Warnke and Helmut Remschmidt and Jutta H{\"u}lsmann and Sven Cichon and Lindgren, \{Cecilia M.\} and Peter Propping and Marco Zucchelli and Andreas Ziegler and Myriam Peyrard-Janvid and Gerd Schulte-K{\"o}rne and N{\"o}then, \{Markus M.\} and Juha Kere",

note = "Funding Information: We are grateful to all investigated individuals for their cooperation in this study. This study was supported by the Deutsche Forschungsgemeinschaft. P.P. was supported by the National Genomic Network of the Bundesministerium f{\"u}r Bildung und Forschung. M.M.N. received support for this work from the Alfried Krupp von Bohlen und Halbach-Stiftung. M.P.-J. is a recipient of a research position from the Swedish Research Council (Vetenskpsr{\aa}det). J.K. is supported by grants from the Swedish Research Council, the Academy of Finland, the Sigrid Jus{\'e}lius Foundation, and the P{\"a}ivikki and Sakari Sohlberg Foundation. Some of the results were obtained by using the program package S.A.G.E., which is supported by U.S. Public Health Service Resource grant RR03655 from the National Center for Research Resources. ",

year = "2006",

month = jan,

doi = "10.1086/498992",

language = "English",

volume = "78",

pages = "52--62",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

publisher = "Cell Press",

number = "1",

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Schumacher, J, Anthoni, H, Dahdouh, F, König, IR, Hillmer, AM, Kluck, N, Manthey, M, Plume, E, Warnke, A, Remschmidt, H, Hülsmann, J, Cichon, S, Lindgren, CM, Propping, P, Zucchelli, M, Ziegler, A, Peyrard-Janvid, M, Schulte-Körne, G, Nöthen, MM & Kere, J 2006, 'Strong genetic evidence of DCDC2 as a susceptibility gene for dyslexia', American Journal of Human Genetics, Jg. 78, Nr. 1, S. 52-62. https://doi.org/10.1086/498992

TY - JOUR

T1 - Strong genetic evidence of DCDC2 as a susceptibility gene for dyslexia

AU - Schumacher, Johannes

AU - Anthoni, Heidi

AU - Dahdouh, Faten

AU - König, Inke R.

AU - Hillmer, Axel M.

AU - Kluck, Nadine

AU - Manthey, Malou

AU - Plume, Ellen

AU - Warnke, Andreas

AU - Remschmidt, Helmut

AU - Hülsmann, Jutta

AU - Cichon, Sven

AU - Lindgren, Cecilia M.

AU - Propping, Peter

AU - Zucchelli, Marco

AU - Ziegler, Andreas

AU - Peyrard-Janvid, Myriam

AU - Schulte-Körne, Gerd

AU - Nöthen, Markus M.

AU - Kere, Juha

N1 - Funding Information: We are grateful to all investigated individuals for their cooperation in this study. This study was supported by the Deutsche Forschungsgemeinschaft. P.P. was supported by the National Genomic Network of the Bundesministerium für Bildung und Forschung. M.M.N. received support for this work from the Alfried Krupp von Bohlen und Halbach-Stiftung. M.P.-J. is a recipient of a research position from the Swedish Research Council (Vetenskpsrådet). J.K. is supported by grants from the Swedish Research Council, the Academy of Finland, the Sigrid Jusélius Foundation, and the Päivikki and Sakari Sohlberg Foundation. Some of the results were obtained by using the program package S.A.G.E., which is supported by U.S. Public Health Service Resource grant RR03655 from the National Center for Research Resources.

PY - 2006/1

Y1 - 2006/1

N2 - We searched for linkage disequilibrium (LD) in 137 triads with dyslexia, using markers that span the most-replicated dyslexia susceptibility region on 6p21-p22, and found association between the disease and markers within the VMP/DCDC2/KAAG1 locus. Detailed refinement of the LD region, involving sequencing and genotyping of additional markers, showed significant association within DCDC2 in single-marker and haplotype analyses. The association appeared to be strongest in severely affected patients. In a second step, the study was extended to include an independent sample of 239 triads with dyslexia, in which the association-in particular, with the severe phenotype of dyslexia-was confirmed. Our expression data showed that DCDC2, which contains a doublecortin homology domain that is possibly involved in cortical neuron migration, is expressed in the fetal and adult CNS, which-together with the hypothesized protein function-is in accordance with findings in dyslexic patients with abnormal neuronal migration and maturation.

AB - We searched for linkage disequilibrium (LD) in 137 triads with dyslexia, using markers that span the most-replicated dyslexia susceptibility region on 6p21-p22, and found association between the disease and markers within the VMP/DCDC2/KAAG1 locus. Detailed refinement of the LD region, involving sequencing and genotyping of additional markers, showed significant association within DCDC2 in single-marker and haplotype analyses. The association appeared to be strongest in severely affected patients. In a second step, the study was extended to include an independent sample of 239 triads with dyslexia, in which the association-in particular, with the severe phenotype of dyslexia-was confirmed. Our expression data showed that DCDC2, which contains a doublecortin homology domain that is possibly involved in cortical neuron migration, is expressed in the fetal and adult CNS, which-together with the hypothesized protein function-is in accordance with findings in dyslexic patients with abnormal neuronal migration and maturation.

UR - https://www.scopus.com/pages/publications/29244468273

U2 - 10.1086/498992

DO - 10.1086/498992

M3 - Journal articles

C2 - 16385449

AN - SCOPUS:29244468273

SN - 0002-9297

VL - 78

SP - 52

EP - 62

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 1

ER -

Strong genetic evidence of DCDC2 as a susceptibility gene for dyslexia

Abstract

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