Genome-wide methylomic analysis of monozygotic twins discordant for adolescent depression.
Genome-wide methylomic analysis of monozygotic twins discordant for adolescent depression.
复制标题
DOI：
10.1016/j.biopsych.2014.04.013
复制
发表时间：
2014-12-15
影响因子：
10.6
通讯作者：
Eley TC
中科院分区：
文献类型：
--
作者：
Dempster EL;Wong CC;Lester KJ;Burrage J;Gregory AM;Mill J;Eley TC
青少年抑郁症是一种常见的神经精神疾病，通常持续到成年，并与包括自杀在内的广泛的不良后果有关。尽管许多研究已经研究了与抑郁症相关的遗传标记，但表观遗传变异的作用仍然相对未被探索。单卵（MZ）双胞胎是从一项青少年双胞胎研究中选择的，该研究旨在调查遗传和环境因素在情绪和行为困难发展中的相互作用。有18对MZ双胞胎，其中一个成员的得分始终高于（组平均值在临床显著范围内）自评抑郁症比其他。我们使用来自Illumina的Infinium HumanMethylation 450 BeadChip评估了双颊细胞DNA中DNA甲基化的全基因组模式。使用waterRmelon软件包进行质量控制和数据预处理。使用考虑DNA甲基化差异的显著性和幅度的分析策略来鉴定差异甲基化探针（DMP）。通过亚硫酸氢盐焦磷酸测序成功验证了最高差异甲基化的DMPs，并在从重度抑郁症患者（n = 14）和匹配的对照受试者（n = 15）获得的死后脑样本中测试了鉴定的DMPs。两个可重复的抑郁症相关的DMPs被确定，包括排名第一，位于STK 32 C，它编码的丝氨酸/苏氨酸激酶，功能未知。我们的数据表明，DNA甲基化的差异是明显的MZ双胞胎不一致的青少年抑郁症和口腔细胞DNA中观察到的一些疾病相关的变化是反映在成人脑组织从个人临床抑郁症。
Adolescent depression is a common neuropsychiatric disorder that often continues into adulthood and is associated with a wide range of poor outcomes including suicide. Although numerous studies have looked at genetic markers associated with depression, the role of epigenetic variation remains relatively unexplored. Monozygotic (MZ) twins were selected from an adolescent twin study designed to investigate the interplay of genetic and environmental factors in the development of emotional and behavioral difficulties. There were 18 pairs of MZ twins identified in which one member scored consistently higher (group mean within the clinically significant range) on self-rated depression than the other. We assessed genome-wide patterns of DNA methylation in twin buccal cell DNA using the Infinium HumanMethylation450 BeadChip from Illumina. Quality control and data preprocessing was undertaken using the wateRmelon package. Differentially methylated probes (DMPs) were identified using an analysis strategy taking into account both the significance and the magnitude of DNA methylation differences. The top differentially methylated DMP was successfully validated by bisulfite-pyrosequencing, and identified DMPs were tested in postmortem brain samples obtained from patients with major depressive disorder (n = 14) and matched control subjects (n = 15). Two reproducible depression-associated DMPs were identified, including the top-ranked DMP that was located within STK32C, which encodes a serine/threonine kinase, of unknown function. Our data indicate that DNA methylation differences are apparent in MZ twins discordant for adolescent depression and that some of the disease-associated variation observed in buccal cell DNA is mirrored in adult brain tissue obtained from individuals with clinical depression.
登录
查看更多内容
影响因子：
3.5
作者：
Dempster EL;Pidsley R;Schalkwyk LC;Owens S;Georgiades A;Kane F;Kalidindi S;Picchioni M;Kravariti E;Toulopoulou T;Murray RM;Mill J
通讯作者：
Mill J
影响因子：
2.5
作者：
Miller, Brooke H.;Schultz, Laura E.;Long, Bradley C.;Pletcher, Mathew T.
通讯作者：
Pletcher, Mathew T.
影响因子：
25
作者：
Elliott, Evan;Ezra-Nevo, Gili;Chen, Alon
通讯作者：
Chen, Alon
影响因子：
11
作者：
Bosker, F. J.;Hartman, C. A.;Nolen, W. A.
通讯作者：
Nolen, W. A.
DOI：
10.1017/s1461145713000102
发表时间：
2013-08-01
影响因子：
4.8
作者：
Melas, Philippe A.;Wei, Yabin;Lavebratt, Catharina
通讯作者：
Lavebratt, Catharina