Epigenome-wide association study of global cortical volumes in generation Scotland: Scottish family health study.
Epigenome-wide association study of global cortical volumes in generation Scotland: Scottish family health study.
复制标题
DOI：
10.1080/15592294.2021.1997404
复制
发表时间：
2022-10
期刊：
影响因子：
3.7
通讯作者：
Whalley, Heather
中科院分区：
文献类型：
--
作者：
Barbu, Miruna Carmen;Harris, Mat;Shen, Xueyi;Aleks, Stolicyn;Green, Claire;Amador, Carmen;Walker, Rosie;Morris, Stewart;Adams, Mark;Sandu, Anca;McNeil, Christopher;Waiter, Gordon;Evans, Kathryn;Campbell, Archie;Wardlaw, Joanna;Steele, Douglas;Murray, Alison;Porteous, David;McIntosh, Andrew;Whalley, Heather
遗传和环境风险因素的复杂相互作用影响与大脑健康和疾病相关的全球大脑结构改变。全球脑成像表型的表观全基因组关联研究（EWAS）有可能揭示大脑健康和疾病的机制，并通过开发风险评分来实现更好的预测分析。我们使用来自两次评估的外周测量的全血DNA甲基化（DNAm）对苏格兰一代的全球脑体积进行了EWAS，（i）基线招募时，MRI评估前约6年（N = 672）和（ii）与MRI评估同时进行（N=565）。基线时的4个CpG与全脑白色物质、总灰质和全脑体积相关（Bonferroni p≤7.41×10−8，β范围= − 1.46 × 10 −6至9.59 × 10−7）。这些CpG被注释为与大脑相关特征有关的基因，包括精神疾病，发育和衰老。我们在对两组EWAS进行的荟萃分析中没有发现与校正节段成像的显著相关性。这些发现揭示了与6年前测量的DNAm相关的全球脑结构变化，表明早期DNAm修饰在脑结构中的潜在作用。虽然并发DNAm与全球脑结构无关，但这里确定的名义上显著的发现为将来在更大的基于人群的样本中研究DNA甲基化与结构脑表型之间的关联提供了理论基础。
A complex interplay of genetic and environmental risk factors influence global brain structural alterations associated with brain health and disease. Epigenome-wide association studies (EWAS) of global brain imaging phenotypes have the potential to reveal the mechanisms of brain health and disease and can lead to better predictive analytics through the development of risk scores. We perform an EWAS of global brain volumes in Generation Scotland using peripherally measured whole blood DNA methylation (DNAm) from two assessments, (i) at baseline recruitment, ~6 years prior to MRI assessment (N = 672) and (ii) concurrent with MRI assessment (N=565). Four CpGs at baseline were associated with global cerebral white matter, total grey matter, and whole-brain volume (Bonferroni p≤7.41×10−8, βrange = −1.46x10−6 to 9.59 × 10−7). These CpGs were annotated to genes implicated in brain-related traits, including psychiatric disorders, development, and ageing. We did not find significant associations in the meta-analysis of the EWAS of the two sets concurrent with imaging at the corrected level. These findings reveal global brain structural changes associated with DNAm measured ~6 years previously, indicating a potential role of early DNAm modifications in brain structure. Although concurrent DNAm was not associated with global brain structure, the nominally significant findings identified here present a rationale for future investigation of associations between DNA methylation and structural brain phenotypes in larger population-based samples.
登录
查看更多内容
影响因子：
16.6
作者：
Day FR;Ong KK;Perry JRB
通讯作者：
Perry JRB
影响因子：
5.3
作者：
Dumitrache, Lavinia C.;McKinnon, Peter J.
通讯作者：
McKinnon, Peter J.
影响因子：
16.6
作者：
Chu AY;Tin A;Schlosser P;Ko YA;Qiu C;Yao C;Joehanes R;Grams ME;Liang L;Gluck CA;Liu C;Coresh J;Hwang SJ;Levy D;Boerwinkle E;Pankow JS;Yang Q;Fornage M;Fox CS;Susztak K;Köttgen A
通讯作者：
Köttgen A
影响因子：
6.2
作者：
Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium
通讯作者：
Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium
影响因子：
--
作者：
Fortin, Jean-Philippe;Fertig, Elana;Hansen, Kasper
通讯作者：
Hansen, Kasper