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18 号染色体上导致阅读障碍的遗传风险变异在德国队列中的研究。

Genetic risk variants for dyslexia on chromosome 18 in a German cohort.

机构信息

Department of Cell Therapy, Fraunhofer Institute for Cell Therapy and Immunology.

出版信息

Genes Brain Behav. 2014 Mar;13(3):350-6. doi: 10.1111/gbb.12118. Epub 2014 Feb 3.

Abstract

Dyslexia is characterized by impaired reading and spelling. The disorder has a prevalence of about 5% in Germany, and a strong hereditary component. Several loci are thought to be involved in the development of dyslexia. Scerri et al. identified eight potential dyslexia-associated single nucleotide polymorphisms (SNPs) in seven genes on chromosome 18 in an English-speaking population. Here, we present an association analysis that explores the relevance of these SNPs in a German population comprising 388 dyslexia cases and 364 control cases. In case-control analysis, three nominal SNP associations were replicated. The major alleles of NEDD4L-rs12606138 and NEDD4L-rs8094327 were risk associated [odds ratio (OR) = 1.35, 95% confidence interval (CI) = 1.0-1.7, P-value = 0.017 and OR = 1.39, 95% CI = 1.1-1.7, P-value = 0.007, respectively], and both SNPs were in strong linkage disequilibrium (r(2)  = 0.95). For MYO5B-rs555879, the minor allele was risk associated (OR = 1.31, 95% CI = 1.1-1.6, P-value = 0.011). The combined analysis of SNP sets using set enrichment analysis revealed a study-wide significant association for three SNPs with susceptibility for dyslexia. In summary, our results substantiate genetic markers in NEDD4L and MYO5B as risk factors for dyslexia and provide first evidence that the relevance of these markers is not restricted to the English language.

摘要

诵读困难症的特征是阅读和拼写障碍。该障碍在德国的患病率约为 5%,具有很强的遗传成分。据认为,有几个基因座参与了诵读困难症的发展。Scerri 等人在一个讲英语的人群中,在 18 号染色体上的 7 个基因中确定了 8 个潜在的与诵读困难症相关的单核苷酸多态性(SNP)。在这里,我们进行了一项关联分析,探索了这些 SNP 在一个由 388 例诵读困难症病例和 364 例对照病例组成的德国人群中的相关性。在病例对照分析中,有 3 个名义 SNP 关联得到了复制。NEDD4L-rs12606138 和 NEDD4L-rs8094327 的主要等位基因与风险相关[比值比(OR)=1.35,95%置信区间(CI)=1.0-1.7,P 值=0.017 和 OR=1.39,95% CI=1.1-1.7,P 值=0.007],并且这两个 SNP 之间存在强连锁不平衡(r(2) =0.95)。对于 MYO5B-rs555879,次要等位基因与风险相关(OR=1.31,95% CI=1.1-1.6,P 值=0.011)。使用集合富集分析对 SNP 集进行的联合分析显示,三个 SNP 与诵读困难症的易感性存在显著关联。总之,我们的结果证实了 NEDD4L 和 MYO5B 中的遗传标记是诵读困难症的风险因素,并首次提供了这些标记的相关性不仅限于英语的证据。

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