Gardner Michelle, Bertranpetit Jaume, Comas David
Unitat de Biologia Evolutiva, Universitat Pompeu Fabra, Doctor Aiguader, Barcelona, Spain.
Am J Med Genet B Neuropsychiatr Genet. 2008 Oct 5;147B(7):1070-5. doi: 10.1002/ajmg.b.30717.
The dopamine and serotonin systems are two of the most important neurotransmitter pathways in the human nervous system and their roles in controlling behavior and mental status are well accepted. Genes from both systems have been widely implicated in psychiatric and behavioral disorders, with numerous reports of associations and almost equally as numerous reports of the failure to replicate a previous finding of association. We investigate a set of 21 dopamine and serotonin genes commonly tested for association with psychiatric disease in a set of 39 worldwide populations representing global genetic diversity to see whether the failure to replicate findings of association may be explained by population based differences in allele frequencies and linkage disequilibrium (LD) in this gene set. We present results demonstrating a surprising homogeneity of the allele frequencies across worldwide populations in these genes. LD both for populations within continent groupings and across continental regions also showed a remarkable similarity. These findings taken together suggest that ethnic differences in these parameters are not major generators of artifacts in genetic association studies of psychiatric disorders with genes from this set. Therefore, factors other than ethnic differences in genetic variation may explain the discrepancies reported among genetic association studies with this set of genes to date. The transferability of tagSNPs defined in the HapMap populations to other worldwide populations was also investigated and found to be high. A list of tagSNPs per gene and continental region is proposed providing a guide for future association studies with these genes.
多巴胺和血清素系统是人类神经系统中两个最重要的神经递质通路，它们在控制行为和精神状态方面的作用已得到广泛认可。来自这两个系统的基因已被广泛认为与精神和行为障碍有关，有大量关于关联的报道，也有几乎同样多关于无法重复先前关联发现的报道。我们在一组代表全球遗传多样性的39个全球人群中，研究了一组通常检测与精神疾病关联的21个多巴胺和血清素基因，以查看关联发现无法重复是否可以用该基因集中基于人群的等位基因频率和连锁不平衡（LD）差异来解释。我们展示的结果表明，这些基因在全球人群中的等位基因频率具有惊人的同质性。大陆组内人群以及跨大陆区域的LD也显示出显著的相似性。综合这些发现表明，在使用该组基因进行精神疾病遗传关联研究时，这些参数中的种族差异并非造成假象的主要因素。因此，除了遗传变异中的种族差异外，其他因素可能解释了迄今为止使用这组基因进行的遗传关联研究中报告的差异。我们还研究了HapMap人群中定义的标签单核苷酸多态性（tagSNP）在其他全球人群中的可转移性，发现其可转移性很高。我们提出了每个基因和大陆区域的tagSNP列表，为未来使用这些基因进行关联研究提供指导。
