The autism spectrum disorders (ASD) are common neuropsychiatric conditions of childhood for which the vast proportion of population risk is attributable to inheritance, and for which there exist few if any replicated biomarkers. This commentary summarizes a set of recent studies involving identical (monozygotic, MZ) twins which, taken together, have significant implications for the search for biomarkers of inherited susceptibility to autism. A first is that variation-in-severity of the condition (above the threshold for clinical diagnosis) appears more strongly influenced by stochastic/non-shared environmental influences than by heredity. Second is that there exist disparate early behavioral predictors of the familial recurrence of autism, which are themselves strongly genetically influenced but largely independent from one another. The nature of these postnatal predictors is that they are trait-like, continuously distributed in the general population, and largely independent from variation in general cognition, thereby reflecting a developmental substructure for familial autism. A corollary of these findings is that autism may arise as a developmental consequence of an allostatic load of earlier-occurring liabilities, indexed by early behavioral endophenotypes, in varying permutations and combinations. The clinical threshold can be viewed as a “tipping point” at which stochastic influences and/or other non-shared environmental influences assert much stronger influence on variation-in-severity (a) than do the genetic factors which contributed to the condition in the first place, and (b) than is observed in typical development. Biomarkers identified on the basis of association with clinical symptom severity in ASD may reflect effects rather than causes of autism. The search for biomarkers of pathogenesis may benefit from a greater focus on traits that predict autism recurrence, among both clinical and general populations. In case–control studies, salient developmental liabilities should be systematically measured in both cases and controls, to avoid the erosion in statistical power (i.e., to detect differences) that can occur if control subjects carry sub-clinical aggregations of the same unmeasured traits that exert causal influences on the development of autism.

中文翻译：

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自闭症生物标志物寻求者的新指南：来自同卵双胞胎研究的更新

自闭症谱系障碍 (ASD) 是儿童时期常见的神经精神疾病，其大部分人口风险可归因于遗传，并且几乎没有复制的生物标志物。这篇评论总结了一组最近涉及同卵（单卵，MZ）双胞胎的研究，这些研究对寻找遗传自闭症易感性的生物标志物具有重要意义。首先是病情严重程度的变化（高于临床诊断的阈值）似乎受随机/非共享环境影响的影响比受遗传影响更大。其次，自闭症家族性复发存在不同的早期行为预测因子，它们本身受到强烈的遗传影响，但在很大程度上相互独立。这些出生后预测因子的性质是它们具有特征样，在一般人群中持续分布，并且在很大程度上独立于一般认知的变化，从而反映了家族性自闭症的发育亚结构。这些发现的一个推论是，自闭症可能是早期发生的责任的平衡负荷的发展结果，由早期行为内表型以不同的排列和组合进行索引。临床阈值可以被视为一个“临界点”，在该临界点上，随机影响和/或其他非共享环境影响对严重性变化 (a) 的影响比导致该疾病的遗传因素强得多。首先，并且 (b) 比在典型开发中观察到的要好。基于与 ASD 临床症状严重程度相关的生物标志物可能反映自闭症的影响而不是原因。寻找发病机制的生物标志物可能会受益于更多地关注预测自闭症复发的特征，在临床和一般人群中。在病例对照研究中，应在病例和对照中系统地测量显着的发展倾向，以避免如果对照受试者携带相同的未测量特征的亚临床聚合，则可能发生统计功效（即，检测差异）的侵蚀。对自闭症的发展产生因果影响。在临床和一般人群中。在病例对照研究中，应在病例和对照中系统地测量显着的发展倾向，以避免如果对照受试者携带相同的未测量特征的亚临床聚合，则可能发生统计功效（即，检测差异）的侵蚀。对自闭症的发展产生因果影响。在临床和一般人群中。在病例对照研究中，应在病例和对照中系统地测量显着的发展倾向，以避免如果对照受试者携带相同的未测量特征的亚临床聚合，则可能发生统计功效（即，检测差异）的侵蚀。对自闭症的发展产生因果影响。