Ziegler Andreas, König Inke R, Deimel Wolfgang, Plume Ellen, Nöthen Markus M, Propping Peter, Kleensang André, Müller-Myhsok Bertram, Warnke Andreas, Remschmidt Helmut, Schulte-Körne Gerd
Institut fur Medizinische Biometrie und Statistik, Universitatsklinikum Schleswig-Holstein, Campus Lubeck, Universitat zu Lubeck, Lubeck, Germany.
Hum Hered. 2005;59(3):136-43. doi: 10.1159/000085572. Epub 2005 May 2.
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.
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.
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.
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.
多项研究已证明诵读困难存在遗传因素。然而，分离分析和连锁分析均显示出相互矛盾的结果，这表明分子遗传学研究需要一个最佳的确定方案。此前，我们认为单先证者同胞对设计（SPSP）是最佳的。因此，本文的目的是证明SPSP设计的实用性以及读写复发风险的估计。
我们通过SPSP设计评估了一个家庭样本中的拼写和阅读能力。招募了287个至少有两个兄弟姐妹及其父母的家庭。根据一个标准差（1SD）差异标准，至少有一个孩子患有拼写障碍。
先证者及其兄弟姐妹在拼写和阅读表型方面的平均值不同。对于先证者，表型拼写的方差较小。随着选择标准更加严格，这些影响变得更强。在60.3%和28.9%的家庭中，两个兄弟姐妹分别满足了拼写和阅读的1SD标准，这表明双先证者同胞对方法的成本效益较低。当对两个兄弟姐妹都应用1SD标准时，拼写的复发风险为4.52（置信区间：4.07 - 4.93）。阅读的复发风险估计值相似。
该研究证明了SPSP设计适用于诵读困难的遗传分析。复发风险估计值可用于确定基因定位研究中的样本量。
