Recent work has highlighted a possible role for altered epigenetic modifications, including differential DNA methylation, in susceptibility to psychiatric illness. Here, we investigate blood-based DNA methylation in a large family where a balanced translocation between chromosomes 1 and 11 shows genome-wide significant linkage to psychiatric illness. Genome-wide DNA methylation was profiled in whole-blood-derived DNA from 41 individuals using the Infinium HumanMethylation450 BeadChip (Illumina Inc., San Diego, CA). We found significant differences in DNA methylation when translocation carriers (n = 17) were compared to related non-carriers (n = 24) at 13 loci. All but one of the 13 significant differentially methylated positions (DMPs) mapped to the regions surrounding the translocation breakpoints. Methylation levels of five DMPs were associated with genotype at SNPs in linkage disequilibrium with the translocation. Two of the five genes harbouring significant DMPs, DISC1 and DUSP10, have been previously shown to be differentially methylated in schizophrenia. Gene Ontology analysis revealed enrichment for terms relating to neuronal function and neurodevelopment among the genes harbouring the most significant DMPs. Differentially methylated region (DMR) analysis highlighted a number of genes from the MHC region, which has been implicated in psychiatric illness previously through genetic studies. We show that inheritance of a translocation linked to major mental illness is associated with differential DNA methylation at loci implicated in neuronal development/function and in psychiatric illness. As genomic rearrangements are over-represented in individuals with psychiatric illness, such analyses may be valuable more widely in the study of these conditions.

最近的研究强调了表观遗传修饰改变（包括差异 DNA 甲基化）在精神疾病易感性中可能发挥的作用。在这里，我们研究了一个大家族中基于血液的 DNA 甲基化，其中 1 号和 11 号染色体之间的平衡易位显示出全基因组范围内与精神疾病的显着联系。使用 Infinium HumanMmethylation450 BeadChip (Illumina Inc., San Diego, CA) 对 41 名个体的全血 DNA 进行了全基因组 DNA 甲基化分析。当易位携带者 ( n = 17) 与相关非携带者 ( n = 24) 在 13 个位点进行比较时，我们发现 DNA 甲基化存在显着差异。除 13 个显着差异甲基化位置 (DMP) 外，其余所有位置都映射到易位断点周围的区域。五个 DMP 的甲基化水平与易位连锁不平衡的 SNP 基因型相关。含有重要 DMP 的五个基因中的两个DISC1和DUSP10先前已被证明在精神分裂症中存在差异甲基化。基因本体分析揭示了含有最重要 DMP 的基因中与神经元功能和神经发育相关的术语的丰富性。差异甲基化区域 (DMR) 分析突出显示了 MHC 区域的许多基因，此前通过遗传学研究发现该区域与精神疾病有关。我们发现，与重大精神疾病相关的易位遗传与神经元发育/功能和精神疾病相关位点的差异 DNA 甲基化有关。 由于基因组重排在精神疾病患者中的比例过高，因此此类分析在这些疾病的研究中可能具有更广泛的价值。