Epigenome-wide association study of human frontal cortex identifies differential methylation in Lewy body pathology.
Epigenome-wide association study of human frontal cortex identifies differential methylation in Lewy body pathology.
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DOI：
10.1038/s41467-022-32619-z
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发表时间：
2022-08-22
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
帕金森病（PD）和路易体痴呆（DLB）是两种进行性疾病，在神经病理学上以神经元内错误折叠的α-突触核蛋白聚集为特征，目前尚无有效的疾病改善治疗方法。为了探讨DNA甲基化变化在PD和DLB发病机制中的作用，我们对322个死后额叶皮质样本进行了表观基因组关联研究（EWAS），并在一组独立的200名供体中复制了结果。我们报告了TMCC 2、SFMBT 2、AKAP 6和PHYHIP附近与Braak Lewy体阶段相关的新的差异甲基化复制位点。差异甲基化探针独立于已知的PD遗传风险等位基因。荟萃分析提供了提示性证据，表明在受PD相关22q11.2缺失影响的染色体区域内存在差异甲基化位点。我们的研究结果阐明了PD和DLB的新疾病途径，并为未来路易体病理学的分子研究提出了假设。帕金森病和路易体痴呆是密切相关的神经退行性疾病，尽管表观遗传相似性并不为人所知。在这里，作者研究路易病理学和DNA甲基化在死后人类额叶皮层，确定差异甲基化基因组位点。
Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are closely related progressive disorders with no available disease-modifying therapy, neuropathologically characterized by intraneuronal aggregates of misfolded α-synuclein. To explore the role of DNA methylation changes in PD and DLB pathogenesis, we performed an epigenome-wide association study (EWAS) of 322 postmortem frontal cortex samples and replicated results in an independent set of 200 donors. We report novel differentially methylated replicating loci associated with Braak Lewy body stage near TMCC2, SFMBT2, AKAP6 and PHYHIP. Differentially methylated probes were independent of known PD genetic risk alleles. Meta-analysis provided suggestive evidence for a differentially methylated locus within the chromosomal region affected by the PD-associated 22q11.2 deletion. Our findings elucidate novel disease pathways in PD and DLB and generate hypotheses for future molecular studies of Lewy body pathology. Parkinson’s disease and dementia with Lewy bodies are closely related neurodegenerative disorders, although the epigenetic similarities are not well known. Here, the authors study Lewy pathology and DNA methylation in postmortem human frontal cortex, identifying differentially methylated genomic loci.
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影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
一类新的ER膜蛋白调节与ER相关的内体裂变。
影响因子：
64.5
作者：
Hoyer MJ;Chitwood PJ;Ebmeier CC;Striepen JF;Qi RZ;Old WM;Voeltz GK
通讯作者：
Voeltz GK
影响因子：
4.2
作者：
Blauwendraat C;Faghri F;Pihlstrom L;Geiger JT;Elbaz A;Lesage S;Corvol JC;May P;Nicolas A;Abramzon Y;Murphy NA;Gibbs JR;Ryten M;Ferrari R;Bras J;Guerreiro R;Williams J;Sims R;Lubbe S;Hernandez DG;Mok KY;Robak L;Campbell RH;Rogaeva E;Traynor BJ;Chia R;Chung SJ;International Parkinson's Disease Genomics Consortium (IPDGC), COURAGE-PD Consortium;Hardy JA;Brice A;Wood NW;Houlden H;Shulman JM;Morris HR;Gasser T;Krüger R;Heutink P;Sharma M;Simón-Sánchez J;Nalls MA;Singleton AB;Scholz SW
通讯作者：
Scholz SW
影响因子：
30.8
作者：
Chia R;Sabir MS;Bandres-Ciga S;Saez-Atienzar S;Reynolds RH;Gustavsson E;Walton RL;Ahmed S;Viollet C;Ding J;Makarious MB;Diez-Fairen M;Portley MK;Shah Z;Abramzon Y;Hernandez DG;Blauwendraat C;Stone DJ;Eicher J;Parkkinen L;Ansorge O;Clark L;Honig LS;Marder K;Lemstra A;St George-Hyslop P;Londos E;Morgan K;Lashley T;Warner TT;Jaunmuktane Z;Galasko D;Santana I;Tienari PJ;Myllykangas L;Oinas M;Cairns NJ;Morris JC;Halliday GM;Van Deerlin VM;Trojanowski JQ;Grassano M;Calvo A;Mora G;Canosa A;Floris G;Bohannan RC;Brett F;Gan-Or Z;Geiger JT;Moore A;May P;Krüger R;Goldstein DS;Lopez G;Tayebi N;Sidransky E;American Genome Center;Norcliffe-Kaufmann L;Palma JA;Kaufmann H;Shakkottai VG;Perkins M;Newell KL;Gasser T;Schulte C;Landi F;Salvi E;Cusi D;Masliah E;Kim RC;Caraway CA;Monuki ES;Brunetti M;Dawson TM;Rosenthal LS;Albert MS;Pletnikova O;Troncoso JC;Flanagan ME;Mao Q;Bigio EH;Rodríguez-Rodríguez E;Infante J;Lage C;González-Aramburu I;Sanchez-Juan P;Ghetti B;Keith J;Black SE;Masellis M;Rogaeva E;Duyckaerts C;Brice A;Lesage S;Xiromerisiou G;Barrett MJ;Tilley BS;Gentleman S;Logroscino G;Serrano GE;Beach TG;McKeith IG;Thomas AJ;Attems J;Morris CM;Palmer L;Love S;Troakes C;Al-Sarraj S;Hodges AK;Aarsland D;Klein G;Kaiser SM;Woltjer R;Pastor P;Bekris LM;Leverenz JB;Besser LM;Kuzma A;Renton AE;Goate A;Bennett DA;Scherzer CR;Morris HR;Ferrari R;Albani D;Pickering-Brown S;Faber K;Kukull WA;Morenas-Rodriguez E;Lleó A;Fortea J;Alcolea D;Clarimon J;Nalls MA;Ferrucci L;Resnick SM;Tanaka T;Foroud TM;Graff-Radford NR;Wszolek ZK;Ferman T;Boeve BF;Hardy JA;Topol EJ;Torkamani A;Singleton AB;Ryten M;Dickson DW;Chiò A;Ross OA;Gibbs JR;Dalgard CL;Traynor BJ;Scholz SW
通讯作者：
Scholz SW
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ