meQTL mapping in the GENOA study reveals genetic determinants of DNA methylation in African Americans.
meQTL mapping in the GENOA study reveals genetic determinants of DNA methylation in African Americans.
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DOI：
10.1038/s41467-023-37961-4
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发表时间：
2023-05-11
影响因子：
16.6
通讯作者：
Zhou, Xiang
中科院分区：
文献类型：
--
作者：
Shang, Lulu;Zhao, Wei;Wang, Yi Zhe;Li, Zheng;Choi, Jerome J.;Kho, Minjung;Mosley, Thomas H.;Kardia, Sharon L. R.;Smith, Jennifer A.;Zhou, Xiang
识别与DNA甲基化变异相关的遗传变异，通常被称为甲基化数量性状基因座（meQTL）定位的分析，是理解表观遗传变异背后的遗传结构的重要第一步。大多数现有的meQTL定位研究都集中在欧洲血统的个体上，在其他人群中代表性不足，特别是缺乏非洲血统人群的大型研究。我们填补了这一关键的知识空白，进行了大规模的顺式meQTL定位研究，在961非洲裔美国人的遗传流行病学网络动脉病（GENOA）的研究。我们在320，965个meCpG中鉴定了总共4，565，687个顺式作用meQTL。我们发现45%的meCpGs具有多个独立的meQTL，这表明甲基化变异潜在的多基因遗传结构。大部分cis-meQTL也与cis-expression QTL（eQTL）共定位在同一群体中。重要的是，确定的cis-meQTL解释了相当大比例（中位数= 24.6%）的甲基化变异。此外，cis-meQTL相关的CpG位点介导了相当大比例（中位数= 24.9%）的SNP效应的基因表达。总的来说，我们的研究结果代表了揭示甲基化和基因表达共同调控的重要一步，促进了对非裔美国人常见疾病的表观遗传和基因调控的功能解释。在这里，作者对来自GENOA研究的961名非洲裔美国人进行了大规模深入的cis-meQTL作图研究，调查了非洲裔美国人甲基化和基因表达的共同调控。
Identifying genetic variants that are associated with variation in DNA methylation, an analysis commonly referred to as methylation quantitative trait locus (meQTL) mapping, is an important first step towards understanding the genetic architecture underlying epigenetic variation. Most existing meQTL mapping studies have focused on individuals of European ancestry and are underrepresented in other populations, with a particular absence of large studies in populations with African ancestry. We fill this critical knowledge gap by performing a large-scale cis-meQTL mapping study in 961 African Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA) study. We identify a total of 4,565,687 cis-acting meQTLs in 320,965 meCpGs. We find that 45% of meCpGs harbor multiple independent meQTLs, suggesting potential polygenic genetic architecture underlying methylation variation. A large percentage of the cis-meQTLs also colocalize with cis-expression QTLs (eQTLs) in the same population. Importantly, the identified cis-meQTLs explain a substantial proportion (median = 24.6%) of methylation variation. In addition, the cis-meQTL associated CpG sites mediate a substantial proportion (median = 24.9%) of SNP effects underlying gene expression. Overall, our results represent an important step toward revealing the co-regulation of methylation and gene expression, facilitating the functional interpretation of epigenetic and gene regulation underlying common diseases in African Americans. Here, the authors performed a large-scale in-depth cis-meQTL mapping study in 961 African Americans from the GENOA study, investigating the co-regulation of methylation and gene expression in African Americans.
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影响因子：
4.4
作者：
Bibikova, Marina;Barnes, Bret;Shen, Richard
通讯作者：
Shen, Richard
遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
DOI：
10.1073/pnas.1115761109
发表时间：
2012-01-24
影响因子：
11.1
作者：
Barreiro, Luis B.;Tailleux, Ludovic;Gilad, Yoav
通讯作者：
Gilad, Yoav
影响因子：
12.3
作者：
Gaunt TR;Shihab HA;Hemani G;Min JL;Woodward G;Lyttleton O;Zheng J;Duggirala A;McArdle WL;Ho K;Ring SM;Evans DM;Davey Smith G;Relton CL
通讯作者：
Relton CL
影响因子：
30.8
作者：
Ehret, Georg B.;Ferreira, Teresa;Chasman, Daniel I.;Jackson, Anne U.;Schmidt, Ellen M.;Johnson, Toby;Thorleifsson, Gudmar;Luan, Jian'an;Donnelly, Louise A.;Kanoni, Stavroula;Petersen, Ann -Kristin;Pihurl, Vasyl;Strawbridge, Rona J.;Shungin, Dmitry;Hughes, Maria F.;Meirelles, Osorio;Kaakinen, Marika;Bouatia-Naji, Nabila;Kristiansson, Kati;Shah, Sonia;Kleber, Marcus E.;Guo, Xiuqing;Lyytikainen, Leo-Pekka;Fava, Cristiano;Eriksson, Nidas;Nolte, Ilja M.;Magnusson, Patrik K.;Salfati, Elias L.;Rallidis, Loukianos S.;Theusch, Elizabeth;Smith, Andrew J. P.;Folkersen, Lasse;Witkowska, Kate;Pers, Tune H.;Joehanes, Roby;Kim, Stuart K.;Lataniotis, Lazaros;Jansen, Rick;Johnson, Andrew D.;Warren, Helen;Kim, Young Jin;Zhao, Wei;Wu, Ying;Tayo, Bamidele O.;Bochud, Murielle;Absher, Devin;Adair, Linda S.;Amin, Najaf;Arkingl, Dan E.;Axelsson, Tomas;Baldassarre, Damian;Balkau, Beverley;Bandinelli, Stefania;Barnes, Michael R.;Barroso, Ines;Bevan, Stephen;Bis, Joshua C.;Bjornsdottir, Gyda;Boehnke, Michael;Boerwinkle, Eric;Bonnycastle, Lori L.;Boomsma, Dorret I.;Bornstein, Stefan R.;Brown, Morris J.;Burnier, Michel;Cabrera, Claudia P.;Chambers, John C.;Chang, I-Shou;Cheng, Ching-Yu;Chines, Peter S.;Chung, Ren-Hua;Collins, Francis S.;Connell, John M.;Doring, Angela;Dallongeville, Jean;Danesh, John;de Faire, Ulf;Delgado, Graciela;Dominiczak, Anna F.;Doney, Alex S. F.;Drenos, Fotios;Edkins, Sarah;Eicher, John D.;Elosua, Roberto;Enroth, Stefan;Erdmann, Jeanette;Eriksson, Per;Esko, Tonu;Evangelou, Evangelos;Evans, Alun;Fai, Tove;Farra, Martin;Felixl, Janine F.;Ferrieres, Jean;Ferrucci, Luigi;Fornage, Myriam;Forrester, Terrence;Franceschinil, Nora;Franco, Oscar H.;Franco-Cereceda, Anders;Fraser, Ross M.;Ganesh, Santhi K.;Gao, He;Gertow, Karl;Gianfagna, Francesco;Gigante, Bruna;Giulianini, Franco;Goe, Anuj;Goodall, Alison H.;Goodarzi, Mark;Gorski, Mathias;Grassler, Jurgen;Groves, Christopher J.;Gudnason, Vilmundur;Gyllensten, Ulf;Hallmans, Goran;Hartikainen, Anna-Liisa;Hassinen, Maija;Havulinna, Aki S.;Hayward, Caroline;Hercberg, Serge;Herzig, Karl-Heinz;Hicks, Andrew A.;Hingorani, Aroon D.;Hirschhorn, Joel N.;Hofmanl, Albert;Holmen, Jostein;Holmen, Oddgeir Lingaas;Hottenga, Jouke-Jan;Howard, Phil;Hsiung, Chao A.;Hunt, Steven C.;Ikram, M. Arfan;Illig, Thomas;Iribarren, Carlos;Jensen, Richard A.;Kahonen, Mika;Kang, Hyun Min;Kathiresan, Sekar;Keating, Brendan J.;Khaw, Kay-Tee;Kim, Yun Kyoung;Kim, Eric;Kivimaki, Mika;Klopp, Norman;Kolovou, Genovefa;Komulainen, Pirjo;Kooner, Jaspal S.;Kosova, Gulum;Krauss, Ronald M.;Kuh, Diana;Kutalik, Zoltan;Kuusisto, Johanna;Kvaloy, Kirsti;Lakka, Timo A.;Lee, Nanette R.;Lee, I-Te;Lee, Wen-Jane;Levy, Daniel;Li, Xiaohui;Liang, Kae-Woei;Lin, Honghuang;Lin, Li;Lindstrom, Jaana;Lobbens, Stephane;Mannisto, Satu;Muller, Gabriele;Muller-Nurasyid, Martina;Mach, Francois;Markus, Hugh S.;Marouli, Eirini;McCarthy, Mark I.;McKenzie, Colin A.;Meneton, Pierre;Menni, Cristina;Metspalu, Andres;Mijatovic, Vladan;Moilanen, Leena;Montasser, May E.;Morris, Andrew D.;Morrison, Alanna C.;Mulas, Antonella;Nagaraja, Ramaiah;Narisu, Narisu;Nikus, Kjell;O'Donnell, Christopher J.;O'Reilly, Paul F.;Ong, Ken K.;Paccaud, Fred;Palmer, Cameron D.;Parsa, Afshin;Pedersen, Nancy L.;Penninx, Brenda W.;Perola, Markus;Peters, Annette;Poulter, Neil;Pramstaller, Peter P.;Psaty, Bruce M.;Quertermous, Thomas;Rao, Dabeeru C.;Rasheed, Asif;Rayner, N. William;Renstrom, Frida;Rettig, Rainer;Rice, Kenneth M.;Roberts, Robert;Rose, Lynda M.;Rossouw, Jacques;Samani, Nilesh J.;Sanna, Serena;Saramies, Jouko;Schunkert, Heribert;Sebert, Sylvain;Sheu, Wayne H-H;Shin, Young-Ah;Sim, Xueling;Smit, Johannes H.;Smith, Albert V.;Sosa, Maria X.;Spector, Tim D.;Stancakova, Alena;Stanton, Alice V.;Stirrups, Kathleen E.;Stringham, Heather M.;Sundstrom, Johan;Swift, Amy J.;Syvanen, Ann-Christine;Tai, E-Shyong;Tanaka, Toshiko;Tarasov, Kirill V.;Teumer, Alexander;Thorsteinsdottir, Unnur;Tobin, Martin D.;Tremoli, Elena;Uitterlinden, Andre G.;Uusitupa, Matti;Vaez, Ahmad;Vaidya, Dhananjay;van Duijn, Cornelia M.;van Iperen, Erik P. A.;Vasan, Ramachandran S.;Verwoert, Germaine C.;Virtamo, Jarmo;Vitart, Veronique;Voight, Benjamin F.;Vollenweider, Peter;Wagner, Aline;Wain, Louise V.;Wareham, Nicholas J.;Watldns, Hugh;Weder, Alan B.;Westra, Harm Jan;Wilks, Rainford;Wilsgaard, Tom;Wilson, James F.;Wong, Tien Y.;Yang, Tsun-Po;Yao, Jie;Yengo, Loic;Zhang, Weihua;Zhao, Jing Hua;Zhu, Xiaofeng;Bovet, Pascal;Cooper, Richard S.;Mohlke, Karen L.;Saleheen, Danish;Lee, Jong-Young;Elliott, Paul;Gierman, Hinco J.;Willer, Cristen J.;Franke, Lude;Hovingh, G. Kees;Taylor, Kent D.;Dedoussis, George;Sever, Peter;Wong, Andrew;Lind, Lars;Assimes, Themistocles L.;Njolstad, Inger;Schwarz, Peter E. H.;Langenberg, Claudia;Snieder, Harold;Caulfield, Mark J.;Melander, E.;Laakso, Markku;Saltevo, Juha;Rauramaa, Rainer;Tuomilehto, Jaakko;Ingelsson, Erik;Lehtimaki, Terho;Hveem, Kristian;Palmas, Walter;Marz, Winfried;Kumar, Meena;Salomaa, Veikko;Chen, Yii-Der I.;Rotter, Jerome I.;Froguel, Philippe;Jarvelin, Marjo-Riitta;Lakatta, Edward G.;Kuulasmaa, Kari;Franks, Paul W.;Hamsten, Anders;Wichmann, H-Erich;Palmer, Colin N. A.;Stefansson, Kari;Ridker, Paul M.;Loos, Ruth J. F.;Chalcravarti, Aravinda;Deloukas, Panos;Morris, Andrew P.;Newton-Cheh, Christopher;Munroe, Patricia B.
通讯作者：
Munroe, Patricia B.