Department of Experimental Psychology, University of Oxford, Oxford OX1 3UD, UK.
Behav Genet. 2010 Sep;40(5):618-29. doi: 10.1007/s10519-010-9381-x. Epub 2010 Jul 18.
Traditionally, autistic spectrum disorder (ASD) and specific language impairment (SLI) are regarded as distinct conditions with separate etiologies. Yet these disorders co-occur at above chance levels, suggesting shared etiology. Simulations, however, show that additive pleiotropic genes cannot account for observed rates of language impairment in relatives, which are higher for probands with SLI than for those with ASD + language impairment. An alternative account is in terms of 'phenomimicry', i.e., language impairment in comorbid cases may be a consequence of ASD risk factors, and different from that seen in SLI. However, this cannot explain why molecular genetic studies have found a common risk genotype for ASD and SLI. This paper explores whether nonadditive genetic influences could account for both family and molecular findings. A modified simulation involving G x G interactions obtained levels of comorbidity and rates of impairment in relatives more consistent with observed values. The simulations further suggest that the shape of distributions of phenotypic trait scores for different genotypes may provide evidence of whether a gene is involved in epistasis.
传统上，自闭症谱系障碍（ASD）和特定语言障碍（SLI）被认为是具有不同病因的独立病症。然而，这些病症的同时发生频率高于偶然水平，表明它们具有共同的病因。然而，模拟表明，加性多效基因无法解释在亲属中观察到的语言障碍发生率，对于 SLI 患者的亲属来说，语言障碍的发生率高于 ASD +语言障碍的亲属。另一种解释是“表型模拟”，即合并症病例中的语言障碍可能是 ASD 风险因素的结果，与 SLI 中观察到的不同。然而，这并不能解释为什么分子遗传学研究发现 ASD 和 SLI 有共同的风险基因型。本文探讨了非加性遗传影响是否可以同时解释家族和分子研究结果。涉及 G x G 相互作用的修改后的模拟获得了与观察值更一致的合并症水平和亲属中损伤率。模拟进一步表明，不同基因型表型特征得分分布的形状可能为基因是否参与上位性提供证据。
