Integrated methylome and phenome study of the circulating proteome reveals markers pertinent to brain health.
Integrated methylome and phenome study of the circulating proteome reveals markers pertinent to brain health.
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DOI：
10.1038/s41467-022-32319-8
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发表时间：
2022-08-09
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
描述甲基化组、蛋白质组和表型组之间的关联可以提供对控制大脑健康的生物学途径的深入了解。在这里，我们报告了一个综合的DNA甲基化和循环蛋白质组的表型研究与大脑健康。进行4058种血浆蛋白的全甲基化组关联研究（N = 774），在针对多重测试调整后鉴定2928种CpG-蛋白关联。这些都是独立的已知的遗传蛋白质数量性状基因座（pQTL）和常见的生活方式的影响。然后对每种蛋白质与15种神经学特征（N = 1，065）进行表型全关联研究，确定191种蛋白质水平与认知评分、脑成像测量或APOE e4状态之间的405种关联。我们发现了35个以前未报道的DNA甲基化特征，用于17个大脑健康的蛋白质标记。我们确定的表观遗传和蛋白质组标记与理解和分层大脑健康有关。描述甲基化组、蛋白质组和表型组之间的关联可以提供对控制大脑健康的生物学途径的深入了解。在这里，大脑健康的血液蛋白质标记物与组学数据相结合，以揭示与这些蛋白质标记物相关的DNA甲基化差异。
Characterising associations between the methylome, proteome and phenome may provide insight into biological pathways governing brain health. Here, we report an integrated DNA methylation and phenotypic study of the circulating proteome in relation to brain health. Methylome-wide association studies of 4058 plasma proteins are performed (N = 774), identifying 2928 CpG-protein associations after adjustment for multiple testing. These are independent of known genetic protein quantitative trait loci (pQTLs) and common lifestyle effects. Phenome-wide association studies of each protein are then performed in relation to 15 neurological traits (N = 1,065), identifying 405 associations between the levels of 191 proteins and cognitive scores, brain imaging measures or APOE e4 status. We uncover 35 previously unreported DNA methylation signatures for 17 protein markers of brain health. The epigenetic and proteomic markers we identify are pertinent to understanding and stratifying brain health. Characterising associations between the methylome, proteome and phenome may provide insight into biological pathways governing brain health. Here, blood protein markers of brain health are integrated with omics data to reveal DNA methylation differences that associate with these protein markers.
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影响因子：
7.7
作者：
Gadd DA;Hillary RF;McCartney DL;Zaghlool SB;Stevenson AJ;Cheng Y;Fawns-Ritchie C;Nangle C;Campbell A;Flaig R;Harris SE;Walker RM;Shi L;Tucker-Drob EM;Gieger C;Peters A;Waldenberger M;Graumann J;McRae AF;Deary IJ;Porteous DJ;Hayward C;Visscher PM;Cox SR;Evans KL;McIntosh AM;Suhre K;Marioni RE
通讯作者：
Marioni RE
影响因子：
3.7
作者：
Gold L;Ayers D;Bertino J;Bock C;Bock A;Brody EN;Carter J;Dalby AB;Eaton BE;Fitzwater T;Flather D;Forbes A;Foreman T;Fowler C;Gawande B;Goss M;Gunn M;Gupta S;Halladay D;Heil J;Heilig J;Hicke B;Husar G;Janjic N;Jarvis T;Jennings S;Katilius E;Keeney TR;Kim N;Koch TH;Kraemer S;Kroiss L;Le N;Levine D;Lindsey W;Lollo B;Mayfield W;Mehan M;Mehler R;Nelson SK;Nelson M;Nieuwlandt D;Nikrad M;Ochsner U;Ostroff RM;Otis M;Parker T;Pietrasiewicz S;Resnicow DI;Rohloff J;Sanders G;Sattin S;Schneider D;Singer B;Stanton M;Sterkel A;Stewart A;Stratford S;Vaught JD;Vrkljan M;Walker JJ;Watrobka M;Waugh S;Weiss A;Wilcox SK;Wolfson A;Wolk SK;Zhang C;Zichi D
通讯作者：
Zichi D
影响因子：
16.6
作者：
Hillary, Robert F.;McCartney, Daniel L.;Marioni, Riccardo E.
通讯作者：
Marioni, Riccardo E.
影响因子：
16.6
作者：
Harris, Sarah E.;Cox, Simon R.;Deary, Ian J.
通讯作者：
Deary, Ian J.
影响因子：
6.8
作者：
Corley, Janie;Cox, Simon R.;Deary, Ian J.
通讯作者：
Deary, Ian J.