Developmental Dyslexia – Recurrence Risk Estimates from a German Bi-Center Study Using the Single Proband Sib Pair DesignZiegler A.a · König I.R.a · Deimel W.b · Plume E.c · Nöthen M.M.d · Propping P.d · Kleensang A.a · Müller-Myhsok B.e · Warnke A.c · Remschmidt H.b · Schulte-Körne G.b
aInstitut für Medizinische Biometrie und Statistik, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Universität zu Lübeck, Lübeck, bKlinik für Psychiatrie und Psychotherapie des Kindes- und Jugendalters, Philipps-Universität Marburg, Marburg, cKlinik und Poliklinik für Kinder- und Jugendpsychiatrie, Julius-Maximilians-Universität Würzburg, Würzburg, dInstitut für Humangenetik, Universität Bonn, Bonn, and eMax-Planck-Institut für Psychiatrie München, München, Germany
Objective: Several studies have demonstrated a genetic component for dyslexia. However, both segregation and linkage analyses show contradictory results pointing at the necessity of an optimal ascertainment scheme for molecular genetic studies. Previously, we have argued that the single proband sib pair design (SPSP) would be optimal. The aims of this paper therefore are to demonstrate the practicability of the SPSP design and the estimation of recurrence risks for reading and writing. Methods: We assessed spelling and reading in a family sample ascertained through the SPSP design. 287 families with at least two siblings and their parents were recruited. At least one child was affected with spelling disorder according to a one standard deviation (1SD) discrepancy criterion. Results: Mean values for probands and their siblings were different for both the spelling and the reading phenotype. For the probands, variances of the phenotype spelling were smaller. These effects became stronger with more extreme selection criteria. Both siblings fulfilled the 1SD criterion for spelling and reading in 60.3 and 28.9% of the families, respectively, indicating a low cost efficiency of the double proband sib pair approach. A recurrence risk of 4.52 (CI: 4.07–4.93) was obtained for spelling when the 1SD criterion was applied to both siblings. Recurrence risk estimates were similar for reading. Conclusion: The study demonstrates the suitability of the SPSP design for genetic analysis of dyslexia. The recurrence risk estimates may be used for determining sample sizes in gene mapping studies.
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