Smith Alicia K, Kilaru Varun, Klengel Torsten, Mercer Kristina B, Bradley Bekh, Conneely Karen N, Ressler Kerry J, Binder Elisabeth B
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia; Genetics and Molecular Biology Program, Emory University, Atlanta, Georgia.
Am J Med Genet B Neuropsychiatr Genet. 2015 Jan;168B(1):36-44. doi: 10.1002/ajmg.b.32278. Epub 2014 Oct 29.
DNA methylation has become increasingly recognized in the etiology of psychiatric disorders. Because brain tissue is not accessible in living humans, epigenetic studies are most often conducted in blood. Saliva is often collected for genotyping studies but is rarely used to examine DNA methylation because the proportion of epithelial cells and leukocytes varies extensively between individuals. The goal of this study was to evaluate whether saliva DNA is informative for studies of psychiatric disorders. DNA methylation (HumanMethylation450 BeadChip) was assessed in saliva and blood samples from 64 adult African Americans. Analyses were conducted using linear regression adjusted for appropriate covariates, including estimated cellular proportions. DNA methylation from brain tissues (cerebellum, frontal cortex, entorhinal cortex, and superior temporal gyrus) was obtained from a publically available dataset. Saliva and blood methylation was clearly distinguishable though there was positive correlation overall. There was little correlation in CpG sites within relevant candidate genes. Correlated CpG sites were more likely to occur in areas of low CpG density (i.e., CpG shores and open seas). There was more variability in CpG sites from saliva than blood, which may reflect its heterogeneity. Finally, DNA methylation in saliva appeared more similar to patterns from each of the brain regions examined overall than methylation in blood. Thus, this study provides a framework for using DNA methylation from saliva and suggests that DNA methylation of saliva may offer distinct opportunities for epidemiological and longitudinal studies of psychiatric traits.
DNA甲基化在精神疾病的病因学中已得到越来越多的认识。由于在活体人类中无法获取脑组织，表观遗传学研究大多在血液中进行。唾液常被收集用于基因分型研究，但很少用于检测DNA甲基化，因为个体之间上皮细胞和白细胞的比例差异很大。本研究的目的是评估唾液DNA是否对精神疾病研究有参考价值。对64名成年非裔美国人的唾液和血液样本进行了DNA甲基化（HumanMethylation450 BeadChip）评估。使用针对适当协变量（包括估计的细胞比例）进行调整的线性回归进行分析。脑组织（小脑、额叶皮质、内嗅皮质和颞上回）的DNA甲基化数据来自一个公开可用的数据集。尽管总体上存在正相关，但唾液和血液中的甲基化明显可区分。相关候选基因内的CpG位点相关性很小。相关的CpG位点更可能出现在低CpG密度区域（即CpG岛岸和开阔海域）。唾液中的CpG位点比血液中的变异性更大，这可能反映了其异质性。最后，总体而言，唾液中的DNA甲基化与所检测的每个脑区的模式比血液中的甲基化更相似。因此，本研究为利用唾液中的DNA甲基化提供了一个框架，并表明唾液的DNA甲基化可能为精神特质的流行病学和纵向研究提供独特的机会。
