Epigenetic signatures relating to disease-associated genotypic burden in familial risk of bipolar disorder.
Epigenetic signatures relating to disease-associated genotypic burden in familial risk of bipolar disorder.
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双相情感障碍家族风险中与疾病相关的基因负担相关的表观遗传学特征。
DOI：
10.1038/s41398-022-02079-6
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发表时间：
2022-08-03
影响因子：
6.8
通讯作者：
Fullerton, Janice M.
中科院分区：
文献类型：
--
作者：
Hesam-Shariati, Sonia;Overs, Bronwyn J.;Roberts, Gloria;Toma, Claudio;Watkeys, Oliver J.;Green, Melissa J.;Pierce, Kerrie D.;Edenberg, Howard J.;Wilcox, Holly C.;Stapp, Emma K.;McInnis, Melvin G.;Hulvershorn, Leslie A.;Nurnberger, John I.;Schofield, Peter R.;Mitchell, Philip B.;Fullerton, Janice M.
环境因素有助于双相情感障碍（BD）的风险，但环境因素如何影响精神病理学在遗传风险升高的背景下的发展是未知的。在此，我们试图确定在BD的高家族风险（HR）的年轻人中BD的多基因风险背景下操作的表观遗传标记。使用Illumina PsychArray和Methylation-450 K或-EPIC BeadChips测定外周血来源的DNA。多基因风险评分（PRS）的计算使用最近的BD，重性抑郁症（MDD）和交叉障碍（8种精神疾病的荟萃分析）的全基因组关联研究的汇总统计。根据HR人群分布中的BD-PRS评分对欧洲血统的无关HR受试者（n = 103）进行分层，并将前两个五分位数（高BD-PRS; n = 41）与后两个五分位数（低BD-PRS; n = 41）进行比较。高BD-PRS层的平均交叉疾病-PRS和MDD-PRS也较高（ANCOVA分别为p = 0.035和p = 0.024）。我们使用线性模型评估了高BD-PRS和低BD-PRS层之间的DNA甲基化差异。VARS 2（一种线粒体氨酰-tRNA合成酶）中的一个差异甲基化探针（cg 00933603; p = 3.54 × 10−7）在多重检验校正后仍显着低甲基化。总体而言，BD-PRS似乎广泛影响表观遗传过程，其中1，183个基因映射到标称DMP（p < 0.05）;这些显示与先前与BD，精神分裂症，时间型和冒险相关的基因收敛。我们在两个独立的样本（分别为n = 54和n = 82）中测试了来自标称DMPs的多甲基化表观遗传图谱，并对家庭环境、索引凝聚力和灵活性的影响进行了探索性评估。这项研究强调了遗传风险和表观遗传因素之间的重要相互作用，值得进一步探讨。
Environmental factors contribute to risk of bipolar disorder (BD), but how environmental factors impact the development of psychopathology within the context of elevated genetic risk is unknown. We herein sought to identify epigenetic signatures operating in the context of polygenic risk for BD in young people at high familial risk (HR) of BD. Peripheral blood-derived DNA was assayed using Illumina PsychArray, and Methylation-450K or -EPIC BeadChips. Polygenic risk scores (PRS) were calculated using summary statistics from recent genome-wide association studies for BD, major depressive disorder (MDD) and cross-disorder (meta-analysis of eight psychiatric disorders). Unrelated HR participants of European ancestry (n = 103) were stratified based on their BD-PRS score within the HR-population distribution, and the top two quintiles (High-BD-PRS; n = 41) compared against the bottom two quintiles (Low-BD-PRS; n = 41). The High-BD-PRS stratum also had higher mean cross-disorder-PRS and MDD-PRS (ANCOVA p = 0.035 and p = 0.024, respectively). We evaluated DNA methylation differences between High-BD-PRS and Low-BD-PRS strata using linear models. One differentially methylated probe (DMP) (cg00933603; p = 3.54 × 10−7) in VARS2, a mitochondrial aminoacyl-tRNA synthetase, remained significantly hypomethylated after multiple-testing correction. Overall, BD-PRS appeared to broadly impact epigenetic processes, with 1,183 genes mapped to nominal DMPs (p < 0.05); these displayed convergence with genes previously associated with BD, schizophrenia, chronotype, and risk taking. We tested poly-methylomic epigenetic profiles derived from nominal DMPs in two independent samples (n = 54 and n = 82, respectively), and conducted an exploratory evaluation of the effects of family environment, indexing cohesion and flexibility. This study highlights an important interplay between heritable risk and epigenetic factors, which warrant further exploration.
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影响因子：
4.8
作者：
Ching CRK;Hibar DP;Gurholt TP;Nunes A;Thomopoulos SI;Abé C;Agartz I;Brouwer RM;Cannon DM;de Zwarte SMC;Eyler LT;Favre P;Hajek T;Haukvik UK;Houenou J;Landén M;Lett TA;McDonald C;Nabulsi L;Patel Y;Pauling ME;Paus T;Radua J;Soeiro-de-Souza MG;Tronchin G;van Haren NEM;Vieta E;Walter H;Zeng LL;Alda M;Almeida J;Alnaes D;Alonso-Lana S;Altimus C;Bauer M;Baune BT;Bearden CE;Bellani M;Benedetti F;Berk M;Bilderbeck AC;Blumberg HP;Bøen E;Bollettini I;Del Mar Bonnin C;Brambilla P;Canales-Rodríguez EJ;Caseras X;Dandash O;Dannlowski U;Delvecchio G;Díaz-Zuluaga AM;Dima D;Duchesnay É;Elvsåshagen T;Fears SC;Frangou S;Fullerton JM;Glahn DC;Goikolea JM;Green MJ;Grotegerd D;Gruber O;Haarman BCM;Henry C;Howells FM;Ives-Deliperi V;Jansen A;Kircher TTJ;Knöchel C;Kramer B;Lafer B;López-Jaramillo C;Machado-Vieira R;MacIntosh BJ;Melloni EMT;Mitchell PB;Nenadic I;Nery F;Nugent AC;Oertel V;Ophoff RA;Ota M;Overs BJ;Pham DL;Phillips ML;Pineda-Zapata JA;Poletti S;Polosan M;Pomarol-Clotet E;Pouchon A;Quidé Y;Rive MM;Roberts G;Ruhe HG;Salvador R;Sarró S;Satterthwaite TD;Schene AH;Sim K;Soares JC;Stäblein M;Stein DJ;Tamnes CK;Thomaidis GV;Upegui CV;Veltman DJ;Wessa M;Westlye LT;Whalley HC;Wolf DH;Wu MJ;Yatham LN;Zarate CA;Thompson PM;Andreassen OA;ENIGMA Bipolar Disorder Working Group
通讯作者：
ENIGMA Bipolar Disorder Working Group
影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
遗传和表观遗传变异对基因调节和剪接的组织特异性作用。
影响因子：
4.5
作者：
Gutierrez-Arcelus M;Ongen H;Lappalainen T;Montgomery SB;Buil A;Yurovsky A;Bryois J;Padioleau I;Romano L;Planchon A;Falconnet E;Bielser D;Gagnebin M;Giger T;Borel C;Letourneau A;Makrythanasis P;Guipponi M;Gehrig C;Antonarakis SE;Dermitzakis ET
通讯作者：
Dermitzakis ET
DOI：
10.1093/bioinformatics/btu848
发表时间：
2015-05-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Euesden J;Lewis CM;O'Reilly PF
通讯作者：
O'Reilly PF
影响因子：
3.5
作者：
Cook, James P.;Mahajan, Anubha;Morris, Andrew P.
通讯作者：
Morris, Andrew P.