Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
Mol Psychiatry. 2018 Aug;23(8):1711-1716. doi: 10.1038/mp.2017.208. Epub 2017 Nov 7.
Despite ethnic differences in allele frequencies of variants in dopaminergic genes associated with dopamine D2/D3 receptor availability (D2R), no study to date has investigated the relationship between genetic ancestry and striatal D2R. Here, we show that ancestry-informative markers significantly predict dorsal striatal D2R in 117 healthy ethnically diverse residents of the New York metropolitan area using Positron Emission Tomography (PET) with [C]raclopride (P<0.0001), while correcting for age, sex, BMI, education, smoking status, and estimated socioeconomic status (ZIP codes). Effects of ethnicity on D2R were not driven by variation in dopaminergic candidate genes. Instead, candidate gene associations with striatal D2R were diminished when correcting for ancestry. These findings imply that future studies investigating D2 receptor genes should covary for genetic ancestry or study homogeneous populations. Moreover, ancestry studies on human neurobiology should control for socioeconomic differences between ethnic groups.
尽管与多巴胺 D2/D3 受体可用性相关的多巴胺能基因变体的等位基因频率在不同种族之间存在差异（D2R），但迄今为止尚无研究调查遗传背景与纹状体 D2R 之间的关系。在这里，我们使用正电子发射断层扫描（PET）与 [C]raclopride（P<0.0001）显示，在来自纽约大都市区的 117 名健康的、种族多样化的居民中，具有遗传信息的标记物可显著预测背侧纹状体 D2R，同时校正年龄、性别、BMI、教育程度、吸烟状况和估计的社会经济地位（邮政编码）。D2R 上的种族影响不是由多巴胺能候选基因的变异驱动的。相反，当校正遗传背景时，候选基因与纹状体 D2R 的关联减弱。这些发现意味着，未来研究 D2 受体基因的研究应考虑遗传背景或研究同一种族人群。此外，人类神经生物学的遗传背景研究应控制不同种族之间的社会经济差异。
