Bailey Julia N, Breidenthal Sherry E, Jorgensen Matthew J, McCracken James T, Fairbanks Lynn A
Center for Primate Neuroethology, Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles, Los Angeles, California 90095, USA.
Psychiatr Genet. 2007 Feb;17(1):23-7. doi: 10.1097/YPG.0b013e32801140f2.
The association of novelty seeking with a repeat polymorphism in the coding region of the dopamine D4 receptor gene (DRD4) has been demonstrated in several human populations, but not in others. The objective of this study was to test the generality of the association in a captive nonhuman primate population of known history, using objective methods for assessing novelty seeking and a pedigree-based association design.
Four hundred and fifty two socially-living vervet monkeys (Cercopithecus aethiops) from a large multigenerational pedigree at the UCLA-VA Vervet Research Colony were studied. Two variants in the 48 base pair repeat in exon III of the DRD4 gene have been found in this population, a six-repeat (92%) and a less common five-repeat (8%). Novelty seeking was measured by the latency to approach a large and potentially threatening novel object placed in the home enclosure. Heritability of novelty seeking and the association of novelty seeking with the DRD4 polymorphism were assessed using variance component modeling as implemented in Sequential Oligogenic Linkage Analysis Routines.
The variance component analysis indicated that the DRD4 variant explained a significant portion of the total variance in novelty seeking. The final model included a significant effect of the DRD4 polymorphism (P=0.03), which explained 13% of the phenotypic variance, and a significant remaining genetic effect (h=0. 467+/-0.095, P<0.0001).
The association of DRD4 with novelty seeking has now been replicated in a nonhuman primate species, the vervet monkey.
多巴胺D4受体基因（DRD4）编码区的重复多态性与寻求新奇行为之间的关联已在多个人类群体中得到证实，但在其他群体中未得到证实。本研究的目的是在一个已知历史的圈养非人类灵长类动物群体中，使用评估寻求新奇行为的客观方法和基于系谱的关联设计，来检验这种关联的普遍性。
对来自加州大学洛杉矶分校-退伍军人事务部黑长尾猴研究群体中一个大型多代系谱的452只群居黑长尾猴（非洲绿猴）进行了研究。在该群体中发现了DRD4基因外显子III中48个碱基对重复序列的两种变体，一种是六重复序列（92%），另一种是较罕见的五重复序列（8%）。通过接近放置在圈舍中的一个大型且可能具有威胁性的新奇物体的潜伏期来测量寻求新奇行为。使用顺序寡基因连锁分析程序中实施的方差成分模型评估寻求新奇行为的遗传力以及寻求新奇行为与DRD4多态性的关联。
方差成分分析表明，DRD4变体解释了寻求新奇行为总方差的很大一部分。最终模型包括DRD4多态性的显著效应（P = 0.03），其解释了13%的表型方差，以及显著的剩余遗传效应（h = 0.467±0.095，P < 0.0001）。
DRD4与寻求新奇行为之间的关联现已在非人类灵长类动物物种——黑长尾猴中得到复制。
