Genome-wide imaging association study implicates functional activity and glial homeostasis of the caudate in smoking addiction.
Genome-wide imaging association study implicates functional activity and glial homeostasis of the caudate in smoking addiction.
复制标题
DOI：
10.1186/s12864-017-4124-5
复制
发表时间：
2017-09-19
期刊：
影响因子：
4.4
通讯作者：
Amos CI
中科院分区：
文献类型：
--
作者：
Qian DC;Molfese DL;Jin JL;Titus AJ;He Y;Li Y;Vaissié M;Viswanath H;Baldwin PR;Krahe R;Salas R;Amos CI
全球每年有近 600 万人死亡和超过 5000 亿美元的医疗费用归因于吸烟。人们进行了大量的研究工作来阐明吸烟成瘾的分子基础并促进戒烟。在这项研究中，我们对 64 名非吸烟者和 42 名吸烟者进行了基因分型并获得了静息态和基于任务的功能磁共振成像。吸烟者在正常吸烟（“饱腹”）和至少 12 小时不吸烟（“戒烟”）后进行成像。虽然戒烟者与不吸烟者在 12 个感兴趣的大脑区域之间的成对静息状态功能连接 (RSFC) 方面没有差异，但涉及饱腹吸烟者尾状核和壳核的 RSFC 与不吸烟者显着不同 (P < 0.01)。对奖励和失望体验期间尾状核和壳核活动的进一步分析表明，奖励 (CR) 期间的尾状核活动与吸烟状况相关 (P = 0.015)。此外，CR 较低的戒烟者经历了更严重的戒断症状 (P = 0.024)，这表明 CR 可能与吸烟冲动有关。通过全基因组关联研究 (GWAS) 确定了基因变异与 CR 之间的关联（根据吸烟状况进行调整）。包含或表现出这些变体尾状核特异性表达调节的基因在描述细胞骨架功能、突触组织和损伤反应的基因本体术语中得到丰富（P < 0.001，FDR < 0.05）。通过整合基因组和成像数据，揭示了对尾状核激活和稳态潜在机制的新见解，这可能会指导新的研究方向，以提高我们对成瘾病理学的理解。本文的在线版本 (10.1186/s12864-017-4124-5) 包含补充材料，可供授权用户使用。
Nearly 6 million deaths and over a half trillion dollars in healthcare costs worldwide are attributed to tobacco smoking each year. Extensive research efforts have been pursued to elucidate the molecular underpinnings of smoking addiction and facilitate cessation. In this study, we genotyped and obtained both resting state and task-based functional magnetic resonance imaging from 64 non-smokers and 42 smokers. Smokers were imaged after having smoked normally (“sated”) and after having not smoked for at least 12 h (“abstinent”). While abstinent smokers did not differ from non-smokers with respect to pairwise resting state functional connectivities (RSFCs) between 12 brain regions of interest, RSFCs involving the caudate and putamen of sated smokers significantly differed from those of non-smokers (P < 0.01). Further analyses of caudate and putamen activity during elicited experiences of reward and disappointment show that caudate activity during reward (CR) correlated with smoking status (P = 0.015). Moreover, abstinent smokers with lower CR experienced greater withdrawal symptoms (P = 0.024), which suggests CR may be related to smoking urges. Associations between genetic variants and CR, adjusted for smoking status, were identified by genome-wide association study (GWAS). Genes containing or exhibiting caudate-specific expression regulation by these variants were enriched within Gene Ontology terms that describe cytoskeleton functions, synaptic organization, and injury response (P < 0.001, FDR < 0.05). By integrating genomic and imaging data, novel insights into potential mechanisms of caudate activation and homeostasis are revealed that may guide new directions of research toward improving our understanding of addiction pathology. The online version of this article (10.1186/s12864-017-4124-5) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
4.4
作者：
Backes C;Rühle F;Stoll M;Haas J;Frese K;Franke A;Lieb W;Wichmann HE;Weis T;Kloos W;Lenhof HP;Meese E;Katus H;Meder B;Keller A
通讯作者：
Keller A
影响因子：
25.8
作者：
Hu, Yuzheng;Salmeron, Betty Jo;Yang, Yihong
通讯作者：
Yang, Yihong
影响因子：
64.8
作者：
Hibar, Derrek P.;Stein, Jason L.;Renteria, Miguel E.;Arias-Vasquez, Alejandro;Desrivieres, Sylvane;Jahanshad, Neda;Toro, Roberto;Wittfeld, Katharina;Abramovic, Lucija;Andersson, Micael;Aribisala, Benjamin S.;Armstrong, Nicola J.;Bernard, Manon;Bohlken, Marc M.;Boks, Marco P.;Bralten, Janita;Brown, Andrew A.;Chakravarty, M. Mallar;Chen, Qiang;Ching, Christopher R. K.;Cuellar-Partida, Gabriel;den Braber, Anouk;Giddaluru, Sudheer;Goldman, Aaron L.;Grimm, Oliver;Guadalupe, Tulio;Hass, Johanna;Woldehawariat, Girma;Holmes, Avram J.;Hoogman, Martine;Janowitz, Deborah;Jia, Tianye;Kim, Sungeun;Klein, Marieke;Kraemer, Bernd;Lee, Phil H.;Loohuis, Loes M. Olde;Luciano, Michelle;Macare, Christine;Mather, Karen A.;Mattheisen, Manuel;Milaneschi, Yuri;Nho, Kwangsik;Papmeyer, Martina;Ramasamy, Adaikalavan;Risacher, Shannon L.;Roiz-Santianez, Roberto;Rose, Emma J.;Salami, Alireza;Saemann, Philipp G.;Schmaal, Lianne;Schork, Andrew J.;Shin, Jean;Strike, Lachlan T.;Teumer, Alexander;van Donkelaar, Marjolein M. J.;van Eijk, Kristel R.;Walters, Raymond K.;Westlye, Lars T.;Whelan, Christopher D.;Winkler, Anderson M.;Zwiers, Marcel P.;Alhusaini, Saud;Athanasiu, Lavinia;Ehrlich, Stefan;Hakobjan, Marina M. H.;Hartberg, Cecilie B.;Haukvik, Unn K.;Heister, Angelien J. G. A. M.;Hoehn, David;Kasperaviciute, Dalia;Liewald, David C. M.;Lopez, Lorna M.;Makkinje, Remco R. R.;Matarin, Mar;Naber, Marlies A. M.;McKay, D. Reese;Needham, Margaret;Nugent, Allison C.;Puetz, Benno;Royle, Natalie A.;Shen, Li;Sprooten, Emma;Trabzuni, Daniah;van der Marel, Saskia S. L.;van Hulzen, Kimm J. E.;Walton, Esther;Wolf, Christiane;Almasy, Laura;Ames, David;Arepalli, Sampath;Assareh, Amelia A.;Bastin, Mark E.;Brodaty, Henry;Bulayeva, Kazima B.;Carless, Melanie A.;Cichon, Sven;Corvin, Aiden;Curran, Joanne E.;Czisch, Michael;de Zubicaray, Greig I.;Dillman, Allissa;Duggirala, Ravi;Dyer, Thomas D.;Erk, Susanne;Fedko, Iryna O.;Ferrucci, Luigi;Foroud, Tatiana M.;Fox, Peter T.;Fukunaga, Masaki;Gibbs, J. Raphael;Goering, Harald H. H.;Green, Robert C.;Guelfi, Sebastian;Hansell, Narelle K.;Hartman, Catharina A.;Hegenscheid, Katrin;Heinz, Andreas;Hernandez, Dena G.;Heslenfeld, Dirk J.;Hoekstra, Pieter J.;Holsboer, Florian;Homuth, Georg;Hottenga, Jouke-Jan;Ikeda, Masashi;Jack, Clifford R., Jr.;Jenkinson, Mark;Johnson, Robert;Kanai, Ryota;Keil, Maria;Kent, Jack W., Jr.;Kochunov, Peter;Kwok, John B.;Lawrie, Stephen M.;Liu, Xinmin;Longo, Dan L.;McMahon, Katie L.;Meisenzah, Eva;Melle, Ingrid;Mahnke, Sebastian;Montgomery, Grant W.;Mostert, Jeanette C.;Muehleisen, Thomas W.;Nalls, Michael A.;Nichols, Thomas E.;Nilsson, Lars G.;Noethen, Markus M.;Ohi, Kazutaka;Olvera, Rene L.;Perez-Iglesias, Rocio;Pike, G. Bruce;Potkin, Steven G.;Reinvang, Ivar;Reppermund, Simone;Rietschel, Marcella;Romanczuk-Seiferth, Nina;Rosen, Glenn D.;Rujescu, Dan;Schnell, Knut;Schofield, Peter R.;Smith, Colin;Steen, Vidar M.;Sussmann, Jessika E.;Thalamuthu, Anbupalam;Toga, Arthur W.;Traynor, Bryan J.;Troncoso, Juan;Turner, Jessica A.;Valdes Hernandez, Maria C.;van't Ent, Dennis;van der Brug, Marcel;van der Wee, Nic J. A.;van Tol, Marie-Jose;Veltman, Dick J.;Wassink, Thomas H.;Westman, Eric;Zielke, Ronald H.;Zonderman, Alan B.;Ashbrook, David G.;Hager, Reinmar;Lu, Lu;McMahon, Francis J.;Morris, Derek W.;Williams, Robert W.;Brunner, Han G.;Buckner, Randy L.;Buitelaar, Jan K.;Cahn, Wiepke;Calhoun, Vince D.;Cavalleri, Gianpiero L.;Crespo-Facorro, Benedicto;Dale, Anders M.;Davies, Gareth E.;Delanty, Norman;Depondt, Chantal;Djurovic, Srdjan;Drevets, Wayne C.;Espeseth, Thomas;Gollub, Randy L.;Ho, Beng-Choon;Hoffman, Wolfgang;Hosten, Norbert;Kahn, Rene S.;Le Hellard, Stephanie;Meyer-Lindenberg, Andreas;Mueller-Myhsok, Bertram;Nauck, Matthias;Nyberg, Lars;Pandolfo, Massimo;Penninx, Brenda W. J. H.;Roffman, Joshua L.;Sisodiya, Sanjay M.;Smoller, Jordan W.;van Bokhoven, Hans;van Haren, Neeltje E. M.;Voelzke, Henry;Walter, Henrik;Weiner, Michael W.;Wen, Wei;White, Tonya;Agartz, Ingrid;Andreassen, Ole A.;Blangero, John;Boomsma, Dorret I.;Brouwer, Rachel M.;Cannon, Dara M.;Cookson, Mark R.;de Geus, Eco J. C.;Deary, Ian J.;Donohoe, Gary;Fernandez, Guillen;Fisher, Simon E.;Francks, Clyde;Glahn, David C.;Grabe, Hans J.;Gruber, Oliver;Hardy, John;Hashimoto, Ryota;Pol, Hilleke E. Hulshoff;Joensson, Erik G.;Kloszewska, Iwona;Lovestone, Simon;Mattay, Venkata S.;Mecocci, Patrizia;McDonald, Colm;McIntosh, Andrew M.;Ophoff, Roel A.;Paus, Tomas;Pausova, Zdenka;Ryten, Mina;Sachdev, Perminder S.;Saykin, Andrew J.;Simmons, Andy;Singleton, Andrew;Soininen, Hilkka;Wardlaw, Joanna M.;Weale, Michael E.;Weinberger, Daniel R.;Adams, Hieab H. H.;Launer, Lenore J.;Seiler, Stephan;Schmidt, Reinhold;Chauhan, Ganesh;Satizabal, Claudia L.;Becker, James T.;Yanek, Lisa;van der Lee, Sven J.;Ebling, Maritza;Fischl, Bruce;Longstreth, W. T., Jr.;Greve, Douglas;Schmidt, Helena;Nyquist, Paul;Vinke, Louis N.;van Duijn, Cornelia M.;Xue, Luting;Mazoyer, Bernard;Bis, Joshua C.;Gudnason, Vilmundur;Seshadri, Sudha;Ikram, M. Arfan;Martin, Nicholas G.;Wright, Margaret J.;Schumann, Gunter;Franke, Barbara;Thompson, Paul M., Jr.;Medland, Sarah E.
通讯作者：
Medland, Sarah E.
DOI：
10.1126/science.1262110
发表时间：
2015-05-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
GTEx Consortium
通讯作者：
GTEx Consortium
影响因子：
4.2
作者：
Froeliger B;McConnell PA;Stankeviciute N;McClure EA;Kalivas PW;Gray KM
通讯作者：
Gray KM