Sanfilippo Paul G, Hammond Christopher J, Staffieri Sandra E, Kearns Lisa S, Melissa Liew S H, Barbour Julie M, Hewitt Alex W, Ge Dongliang, Snieder Harold, Mackinnon Jane R, Brown Shayne A, Lorenz Birgit, Spector Tim D, Martin Nicholas G, Wilmer Jeremy B, Mackey David A
Centre for Eye Research Australia, Department of Ophthalmology, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Victoria, Australia.
Twin Res Hum Genet. 2012 Oct;15(5):624-30. doi: 10.1017/thg.2012.22. Epub 2012 Jun 13.
Strabismus represents a complex oculomotor disorder characterized by the deviation of one or both eyes and poor vision. A more sophisticated understanding of the genetic liability of strabismus is required to guide searches for associated molecular variants. In this classical twin study of 1,462 twin pairs, we examined the relative influence of genes and environment in comitant strabismus, and the degree to which these influences can be explained by factors in common with refractive error. Participants were examined for the presence of latent ('phoria') and manifest ('tropia') strabismus using cover-uncover and alternate cover tests. Two phenotypes were distinguished: eso-deviation (esophoria and esotropia) and exo-deviation (exophoria and exotropia). Structural equation modeling was subsequently employed to partition the observed phenotypic variation in the twin data into specific variance components. The prevalence of eso-deviation and exo-deviation was 8.6% and 20.7%, respectively. For eso-deviation, the polychoric correlation was significantly greater in monozygotic (MZ) (r = 0.65) compared to dizygotic (DZ) twin pairs (r = 0.33), suggesting a genetic role (p = .003). There was no significant difference in polychoric correlation between MZ (r = 0.55) and DZ twin pairs (r = 0.53) for exo-deviation (p = .86), implying that genetic factors do not play a significant role in the etiology of exo-deviation. The heritability of an eso-deviation was 0.64 (95% CI 0.50-0.75). The additive genetic correlation for eso-deviation and refractive error was 0.13 and the bivariate heritability (i.e., shared variance) was less than 1%, suggesting negligible shared genetic effect. This study documents a substantial heritability of 64% for eso-deviation, yet no corresponding heritability for exo-deviation, suggesting that the genetic contribution to strabismus may be specific to eso-deviation. Future studies are now needed to identify the genes associated with eso-deviation and unravel their mechanisms of action.
斜视是一种复杂的眼球运动障碍，其特征为一只或两只眼睛出现偏斜以及视力不佳。需要对斜视的遗传易感性有更深入的了解，以指导对相关分子变异的搜索。在这项对1462对双胞胎进行的经典双胞胎研究中，我们研究了基因和环境在共同性斜视中的相对影响，以及这些影响在多大程度上可以由与屈光不正的共同因素来解释。使用遮盖-去遮盖和交替遮盖试验检查参与者是否存在潜在性（“隐斜”）和显性（“显斜”）斜视。区分了两种表型：内斜视（内隐斜和内斜视）和外斜视（外隐斜和外斜视）。随后采用结构方程模型将双胞胎数据中观察到的表型变异划分为特定的方差成分。内斜视和外斜视的患病率分别为8.6%和20.7%。对于内斜视，单卵双胞胎（MZ）的多列相关系数（r = 0.65）显著高于双卵双胞胎（DZ）（r = 0.33），表明存在遗传作用（p = 0.003）。外斜视的MZ（r = 0.55）和DZ双胞胎对（r = 0.53）之间的多列相关系数没有显著差异（p = 0.86），这意味着遗传因素在外斜视的病因中不起重要作用。内斜视的遗传度为0.64（95%置信区间0.50 - 0.75）。内斜视与屈光不正的加性遗传相关系数为0.13，双变量遗传度（即共享方差）小于1%，表明共享遗传效应可忽略不计。这项研究记录了内斜视的遗传度高达64%，而外斜视则没有相应的遗传度，这表明斜视的遗传贡献可能对内斜视具有特异性。现在需要进一步的研究来确定与内斜视相关的基因并阐明其作用机制。
