The Classical Twin Method (CTM) compares the similarity of monozygotic (MZ) twins with that of dizygotic (DZ) twins to make inferences about the relative importance of genes and environment in the etiology of individual differences. The design has been applied to thousands of traits across the biomedical, behavioral and social sciences and is arguably the most widely used natural experiment known to science. The fundamental assumption of the CTM is that trait relevant environmental covariation within MZ pairs is the same as that found within DZ pairs, so that zygosity differences in within-pair variance must be due to genetic factors uncontaminated by the environment. This equal environments assumption (EEA) has been, and still is hotly contested, and has been mentioned as a possible contributing factor to the missing heritability conundrum. In this manuscript, we introduce a new model for testing the EEA, which we call the Augmented Classical Twin Design which uses identity by descent (IBD) sharing between DZ twin pairs to estimate separate environmental variance components for MZ and DZ twin pairs, and provides a test of whether these are equal. We show through simulation that given large samples of DZ twin pairs, the model provides unbiased estimates of variance components and valid tests of the EEA under strong assumptions (e.g. no epistatic variance, IBD sharing in DZ twins estimated accurately etc.) which may not hold in reality. Sample sizes in excess of 50,000 DZ twin pairs with genome-wide genetic data are likely to be required in order to detect substantial violations of the EEA with moderate power. Consequently, we recommend that the Augmented Classical Twin Design only be applied to datasets with very large numbers of DZ twin pairs (> 50,000 DZ twin pairs), and given the strong assumptions relating to the absence of epistatic variance, appropriate caution be exercised regarding interpretation of the results.

经典双胞胎方法 (CTM) 比较单卵 (MZ) 双胞胎与异卵 (DZ) 双胞胎的相似性，以推断基因和环境在个体差异病因学中的相对重要性。该设计已应用于生物医学、行为和社会科学的数千种特征，可以说是科学界已知使用最广泛的自然实验。CTM 的基本假设是 MZ 对内的性状相关环境协变与 DZ 对内发现的相同，因此对内方差的接合性差异必须是由于未受环境污染的遗传因素造成的。这种平等环境假设 (EEA) 一直并且仍然受到激烈争论，并被认为是导致遗漏遗传难题的可能因素。在这份手稿中，我们引入了一种用于测试 EEA 的新模型，我们称之为增强经典双胞胎设计，它使用 DZ 双胞胎之间的下降身份 (IBD) 共享来估计 MZ 和 DZ 双胞胎对的单独环境方差分量，并提供测试它们是否相等。我们通过模拟表明，给定 DZ 双胞胎的大样本，该模型提供了方差分量的无偏估计和 EEA 在强假设下的有效检验（例如，没有上位方差、准确估计的 DZ 双胞胎中的 IBD 共享等）可能不成立。事实上。可能需要超过 50,000 对具有全基因组遗传数据的 DZ 双胞胎的样本量，以便以中等能力检测严重违反 EEA 的行为。最后，