State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China.
PLoS One. 2011;6(7):e21636. doi: 10.1371/journal.pone.0021636. Epub 2011 Jul 13.
Traditional behavioral genetic studies (e.g., twin, adoption studies) have shown that human personality has moderate to high heritability, but recent molecular behavioral genetic studies have failed to identify quantitative trait loci (QTL) with consistent effects. The current study adopted a multi-step approach (ANOVA followed by multiple regression and permutation) to assess the cumulative effects of multiple QTLs. Using a system-level (dopamine system) genetic approach, we investigated a personality trait deeply rooted in the nervous system (the Highly Sensitive Personality, HSP). 480 healthy Chinese college students were given the HSP scale and genotyped for 98 representative polymorphisms in all major dopamine neurotransmitter genes. In addition, two environment factors (stressful life events and parental warmth) that have been implicated for their contributions to personality development were included to investigate their relative contributions as compared to genetic factors. In Step 1, using ANOVA, we identified 10 polymorphisms that made statistically significant contributions to HSP. In Step 2, these polymorphism's main effects and interactions were assessed using multiple regression. This model accounted for 15% of the variance of HSP (p<0.001). Recent stressful life events accounted for an additional 2% of the variance. Finally, permutation analyses ascertained the probability of obtaining these findings by chance to be very low, p ranging from 0.001 to 0.006. Dividing these loci by the subsystems of dopamine synthesis, degradation/transport, receptor and modulation, we found that the modulation and receptor subsystems made the most significant contribution to HSP. The results of this study demonstrate the utility of a multi-step neuronal system-level approach in assessing genetic contributions to individual differences in human behavior. It can potentially bridge the gap between the high heritability estimates based on traditional behavioral genetics and the lack of reproducible genetic effects observed currently from molecular genetic studies.
传统的行为遗传学研究（例如双胞胎、收养研究）表明，人类个性具有中等至高度的遗传性，但最近的分子行为遗传学研究未能确定具有一致影响的数量性状基因座（QTL）。本研究采用多步方法（方差分析后进行多元回归和置换检验）来评估多个 QTL 的累积效应。我们采用系统水平（多巴胺系统）遗传方法，研究了一种深深植根于神经系统的个性特征（高度敏感人格，HSP）。480 名健康的中国大学生接受了 HSP 量表的测试，并对所有主要多巴胺神经递质基因中的 98 个代表性多态性进行了基因分型。此外，还纳入了两个环境因素（压力生活事件和父母温暖），因为它们对个性发展有贡献，以研究它们与遗传因素相比的相对贡献。在步骤 1 中，我们使用方差分析确定了 10 个对 HSP 有统计学显著贡献的多态性。在步骤 2 中，我们使用多元回归评估了这些多态性的主要效应和相互作用。该模型解释了 HSP 变异的 15%（p<0.001）。最近的压力生活事件又解释了另外 2%的变异。最后，置换检验确定了获得这些发现的可能性非常低，p 值范围从 0.001 到 0.006。将这些基因座按多巴胺合成、降解/转运、受体和调节的亚系统划分，我们发现调节和受体亚系统对 HSP 的贡献最大。本研究的结果表明，采用多步神经元系统水平方法评估遗传对人类行为个体差异的贡献是有效的。它可能有助于弥合基于传统行为遗传学的高遗传性估计与目前从分子遗传学研究中观察到的缺乏可重复遗传效应之间的差距。
