Segal N L, Feng R, McGuire S A, Allison D B, Miller S
Department of Psychology, California State University, 800 N. State College Blvd., Fullerton, CA 92834, USA.
Int J Obes (Lond). 2009 Jan;33(1):37-41. doi: 10.1038/ijo.2008.228. Epub 2008 Nov 25.
Earlier studies have established that a substantial percentage of variance in obesity-related phenotypes is explained by genetic components. However, only one study has used both virtual twins (VTs) and biological twins and was able to simultaneously estimate additive genetic, non-additive genetic, shared environmental and unshared environmental components in body mass index (BMI). Our current goal was to re-estimate four components of variance in BMI, applying a more rigorous model to biological and virtual multiples with additional data. Virtual multiples share the same family environment, offering unique opportunities to estimate common environmental influence on phenotypes that cannot be separated from the non-additive genetic component using only biological multiples.
Data included 929 individuals from 164 monozygotic twin pairs, 156 dizygotic twin pairs, five triplet sets, one quadruplet set, 128 VT pairs, two virtual triplet sets and two virtual quadruplet sets. Virtual multiples consist of one biological child (or twins or triplets) plus one same-aged adoptee who are all raised together since infancy. We estimated the additive genetic, non-additive genetic, shared environmental and unshared random components in BMI using a linear mixed model. The analysis was adjusted for age, age(2), age(3), height, height(2), height(3), gender and race.
Both non-additive genetic and common environmental contributions were significant in our model (P-values<0.0001). No significant additive genetic contribution was found. In all, 63.6% (95% confidence interval (CI) 51.8-75.3%) of the total variance of BMI was explained by a non-additive genetic component, 25.7% (95% CI 13.8-37.5%) by a common environmental component and the remaining 10.7% by an unshared component.
Our results suggest that genetic components play an essential role in BMI and that common environmental factors such as diet or exercise also affect BMI. This conclusion is consistent with our earlier study using a smaller sample and shows the utility of virtual multiples for separating non-additive genetic variance from common environmental variance.
早期研究表明,肥胖相关表型的很大一部分变异可由遗传因素解释。然而,仅有一项研究同时使用了虚拟双胞胎(VTs)和生物学双胞胎,并能够同时估计体重指数(BMI)中的加性遗传、非加性遗传、共享环境和非共享环境成分。我们当前的目标是重新估计BMI变异的四个成分,对生物学和虚拟多胞胎应用更严格的模型并使用额外数据。虚拟多胞胎共享相同的家庭环境,为估计共同环境对表型的影响提供了独特机会,而仅使用生物学多胞胎无法将这种影响与非加性遗传成分区分开来。
数据包括来自164对同卵双胞胎、156对异卵双胞胎、5组三胞胎、1组四胞胎、128对VT双胞胎、2组虚拟三胞胎和2组虚拟四胞胎的929名个体。虚拟多胞胎由一名生物学孩子(或双胞胎或三胞胎)加上一名同龄被收养者组成,他们自婴儿期起就一起抚养长大。我们使用线性混合模型估计BMI中的加性遗传、非加性遗传、共享环境和非共享随机成分。分析针对年龄、年龄²、年龄³、身高、身高²、身高³、性别和种族进行了调整。
在我们的模型中,非加性遗传和共同环境贡献均具有显著性(P值<0.0001)。未发现显著的加性遗传贡献。总体而言,BMI总变异的63.6%(95%置信区间(CI)51.8 - 75.3%)由非加性遗传成分解释,25.7%(95%CI 13.8 - 37.5%)由共同环境成分解释,其余10.7%由非共享成分解释。
我们的结果表明,遗传成分在BMI中起重要作用,饮食或运动等共同环境因素也会影响BMI。这一结论与我们早期使用较小样本的研究一致,并显示了虚拟多胞胎在区分非加性遗传变异和共同环境变异方面的效用。