المؤلفون: Chen, J. (Ji), Spracklen, C. N. (Cassandra N.), Marenne, G. (Gaelle), Varshney, A. (Arushi), Corbin, L. J. (Laura J.), Luan, J. (Jian'an), Willems, S. M. (Sara M.), Wu, Y. (Ying), Zhang, X. (Xiaoshuai), Horikoshi, M. (Momoko), Boutin, T. S. (Thibaud S.), Magi, R. (Reedik), Waage, J. (Johannes), Li-Gao, R. (Ruifang), Chan, K. H. (Kei Hang Katie), Yao, J. (Jie), Anasanti, M. D. (Mila D.), Chu, A. Y. (Audrey Y.), Claringbould, A. (Annique), Heikkinen, J. (Jani), Hong, J. (Jaeyoung), Hottenga, J.-J. (Jouke-Jan), Huo, S. (Shaofeng), Kaakinen, M. A. (Marika A.), Louie, T. (Tin), Maerz, W. (Winfried), Moreno-Macias, H. (Hortensia), Ndungu, A. (Anne), Nelson, S. C. (Sarah C.), Nolte, I. M. (Ilja M.), North, K. E. (Kari E.), Raulerson, C. K. (Chelsea K.), Ray, D. (Debashree), Rohde, R. (Rebecca), Rybin, D. (Denis), Schurmann, C. (Claudia), Sim, X. (Xueling), Southam, L. (Lorraine), Stewart, I. D. (Isobel D.), Wang, C. A. (Carol A.), Wang, Y. (Yujie), Wu, P. (Peitao), Zhang, W. (Weihua), Ahluwalia, T. S. (Tarunveer S.), Appel, E. V. (Emil V. R.), Bielak, L. F. (Lawrence F.), Brody, J. A. (Jennifer A.), Burtt, N. P. (Noel P.), Cabrera, C. P. (Claudia P.), Cade, B. E. (Brian E.), Chai, J. F. (Jin Fang), Chai, X. (Xiaoran), Chang, L.-C. (Li-Ching), Chen, C.-H. (Chien-Hsiun), Chen, B. H. (Brian H.), Chitrala, K. N. (Kumaraswamy Naidu), Chiu, Y.-F. (Yen-Feng), de Haan, H. G. (Hugoline G.), Delgado, G. E. (Graciela E.), Demirkan, A. (Ayse), Duan, Q. (Qing), Engmann, J. (Jorgen), Fatumo, S. A. (Segun A.), Gayan, J. (Javier), Giulianini, F. (Franco), Gong, J. H. (Jung Ho), Gustafsson, S. (Stefan), Hai, Y. (Yang), Hartwig, F. P. (Fernando P.), He, J. (Jing), Heianza, Y. (Yoriko), Huang, T. (Tao), Huerta-Chagoya, A. (Alicia), Hwang, M. Y. (Mi Yeong), Jensen, R. A. (Richard A.), Kawaguchi, T. (Takahisa), Kentistou, K. A. (Katherine A.), Kim, Y. J. (Young Jin), Kleber, M. E. (Marcus E.), Kooner, I. K. (Ishminder K.), Lai, S. (Shuiqing), Lange, L. A. (Leslie A.), Langefeld, C. D. (Carl D.), Lauzon, M. (Marie), Li, M. (Man), Ligthart, S. (Symen), Liu, J. (Jun), Loh, M. (Marie), Long, J. (Jirong), Lyssenko, V. (Valeriya), Mangino, M. (Massimo), Marzi, C. (Carola), Montasser, M. E. (May E.), Nag, A. (Abhishek), Nakatochi, M. (Masahiro), Noce, D. (Damia), Noordam, R. (Raymond), Pistis, G. (Giorgio), Preuss, M. (Michael), Raffield, L. (Laura), Rasmussen-Torvik, L. J. (Laura J.), Rich, S. S. (Stephen S.), Robertson, N. R. (Neil R.), Rueedi, R. (Rico), Ryan, K. (Kathleen), Sanna, S. (Serena), Saxena, R. (Richa), Schraut, K. E. (Katharina E.), Sennblad, B. (Bengt), Setoh, K. (Kazuya), Smith, A. V. (Albert V.), Sparso, T. (Thomas), Strawbridge, R. J. (Rona J.), Takeuchi, F. (Fumihiko), Tan, J. (Jingyi), Trompet, S. (Stella), van den Akker, E. (Erik), van der Most, P. J. (Peter J.), Verweij, N. (Niek), Vogel, M. (Mandy), Wang, H. (Heming), Wang, C. (Chaolong), Wang, N. (Nan), Warren, H. R. (Helen R.), Wen, W. (Wanqing), Wilsgaard, T. (Tom), Wong, A. (Andrew), Wood, A. R. (Andrew R.), Xie, T. (Tian), Zafarmand, M. H. (Mohammad Hadi), Zhao, J.-H. (Jing-Hua), Zhao, W. (Wei), Amin, N. (Najaf), Arzumanyan, Z. (Zorayr), Astrup, A. (Arne), Bakker, S. J. (Stephan J. L.), Baldassarre, D. (Damiano), Beekman, M. (Marian), Bergman, R. N. (Richard N.), Bertoni, A. (Alain), Blueher, M. (Matthias), Bonnycastle, L. L. (Lori L.), Bornstein, S. R. (Stefan R.), Bowden, D. W. (Donald W.), Cai, Q. (Qiuyin), Campbell, A. (Archie), Campbell, H. (Harry), Chang, Y. C. (Yi Cheng), de Geus, E. J. (Eco J. C.), Dehghan, A. (Abbas), Du, S. (Shufa), Eiriksdottir, G. (Gudny), Farmaki, A. E. (Aliki Eleni), Franberg, M. (Mattias), Fuchsberger, C. (Christian), Gao, Y. (Yutang), Gjesing, A. P. (Anette P.), Goel, A. (Anuj), Han, S. (Sohee), Hartman, C. A. (Catharina A.), Herder, C. (Christian), Hicks, A. A. (Andrew A.), Hsieh, C.-H. (Chang-Hsun), Hsueh, W. A. (Willa A.), Ichihara, S. (Sahoko), Igase, M. (Michiya), Ikram, M. A. (M. Arfan), Johnson, W. C. (W. Craig), Jorgensen, M. E. (Marit E.), Joshi, P. K. (Peter K.), Kalyani, R. R. (Rita R.), Kandeel, F. R. (Fouad R.), Katsuya, T. (Tomohiro), Khor, C. C. (Chiea Chuen), Kiess, W. (Wieland), Kolcic, I. (Ivana), Kuulasmaa, T. (Teemu), Kuusisto, J. (Johanna), Lall, K. (Kristi), Lam, K. (Kelvin), Lawlor, D. A. (Deborah A.), Lee, N. R. (Nanette R.), Lemaitre, R. N. (Rozenn N.), Li, H. (Honglan), Lin, S.-Y. (Shih-Yi), Lindstrom, J. (Jaana), Linneberg, A. (Allan), Liu, J. (Jianjun), Lorenzo, C. (Carlos), Matsubara, T. (Tatsuaki), Matsuda, F. (Fumihiko), Mingrone, G. (Geltrude), Mooijaart, S. (Simon), Moon, S. (Sanghoon), Nabika, T. (Toru), Nadkarni, G. N. (Girish N.), Nadler, J. L. (Jerry L.), Nelis, M. (Mari), Neville, M. J. (Matt J.), Norris, J. M. (Jill M.), Ohyagi, Y. (Yasumasa), Peters, A. (Annette), Peyser, P. A. (Patricia A.), Polasek, O. (Ozren), Qi, Q. (Qibin), Raven, D. (Dennis), Reilly, D. F. (Dermot F.), Reiner, A. (Alex), Rivideneira, F. (Fernando), Roll, K. (Kathryn), Rudan, I. (Igor), Sabanayagam, C. (Charumathi), Sandow, K. (Kevin), Sattar, N. (Naveed), Schuermann, A. (Annette), Shi, J. (Jinxiu), Stringham, H. M. (Heather M.), Taylor, K. D. (Kent D.), Teslovich, T. M. (Tanya M.), Thuesen, B. (Betina), Timmers, P. R. (Paul R. H. J.), Tremoli, E. (Elena), Tsai, M. Y. (Michael Y.), Uitterlinden, A. (Andre), van Dam, R. M. (Rob M.), van Heemst, D. (Diana), van Hylckama Vlieg, A. (Astrid), van Vliet-Ostaptchouk, J. V. (Jana V.), Vangipurapu, J. (Jagadish), Vestergaard, H. (Henrik), Wang, T. (Tao), Willems van Dijk, K. (Ko), Zemunik, T. (Tatijana), Abecasis, G. R. (Goncalo R.), Adair, L. S. (Linda S.), Aguilar-Salinas, C. A. (Carlos Alberto), Alarcon-Riquelme, M. E. (Marta E.), An, P. (Ping), Aviles-Santa, L. (Larissa), Becker, D. M. (Diane M.), Beilin, L. J. (Lawrence J.), Bergmann, S. (Sven), Bisgaard, H. (Hans), Black, C. (Corri), Boehnke, M. (Michael), Boerwinkle, E. (Eric), Boehm, B. O. (Bernhard O.), Bonnelykke, K. (Klaus), Boomsma, D. I. (D. I.), Bottinger, E. P. (Erwin P.), Buchanan, T. A. (Thomas A.), Canouil, M. (Mickael), Caulfield, M. J. (Mark J.), Chambers, J. C. (John C.), Chasman, D. I. (Daniel I.), Chen, Y. I. (Yii-Der Ida), Cheng, C.-Y. (Ching-Yu), Collins, F. S. (Francis S.), Correa, A. (Adolfo), Cucca, F. (Francesco), de Silva, H. J. (H. Janaka), Dedoussis, G. (George), Elmstahl, S. (Solve), Evans, M. K. (Michele K.), Ferrannini, E. (Ele), Ferrucci, L. (Luigi), Florez, J. C. (Jose C.), Franks, P. W. (Paul W.), Frayling, T. M. (Timothy M.), Froguel, P. (Philippe), Gigante, B. (Bruna), Goodarzi, M. O. (Mark O.), Gordon-Larsen, P. (Penny), Grallert, H. (Harald), Grarup, N. (Niels), Grimsgaard, S. (Sameline), Groop, L. (Leif), Gudnason, V. (Vilmundur), Guo, X. (Xiuqing), Hamsten, A. (Anders), Hansen, T. (Torben), Hayward, C. (Caroline), Heckbert, S. R. (Susan R.), Horta, B. L. (Bernardo L.), Huang, W. (Wei), Ingelsson, E. (Erik), James, P. S. (Pankow S.), Järvelin, M.-R. (Marjo-Ritta), Jonas, J. B. (Jost B.), Jukema, J. W. (J. Wouter), Kaleebu, P. (Pontiano), Kaplan, R. (Robert), Kardia, S. L. (Sharon L. R.), Kato, N. (Norihiro), Keinanen-Kiukaanniemi, S. M. (Sirkka M.), Kim, B.-J. (Bong-Jo), Kivimaki, M. (Mika), Koistinen, H. A. (Heikki A.), Kooner, J. S. (Jaspal S.), Koerner, A. (Antje), Kovacs, P. (Peter), Kuh, D. (Diana), Kumari, M. (Meena), Kutalik, Z. (Zoltan), Laakso, M. (Markku), Lakka, T. A. (Timo A.), Launer, L. J. (Lenore J.), Leander, K. (Karin), Li, H. (Huaixing), Lin, X. (Xu), Lind, L. (Lars), Lindgren, C. (Cecilia), Liu, S. (Simin), Loos, R. J. (Ruth J. F.), Magnusson, P. K. (Patrik K. E.), Mahajan, A. (Anubha), Metspalu, A. (Andres), Mook-Kanamori, D. O. (Dennis O.), Mori, T. A. (Trevor A.), Munroe, P. B. (Patricia B.), Njolstad, I. (Inger), O'Connell, J. R. (Jeffrey R.), Oldehinkel, A. J. (Albertine J.), Ong, K. K. (Ken K.), Padmanabhan, S. (Sandosh), Palmer, C. N. (Colin N. A.), Palmer, N. D. (Nicholette D.), Pedersen, O. (Oluf), Pennell, C. E. (Craig E.), Porteous, D. J. (David J.), Pramstaller, P. P. (Peter P.), Province, M. A. (Michael A.), Psaty, B. M. (Bruce M.), Qi, L. (Lu), Raffel, L. J. (Leslie J.), Rauramaa, R. (Rainer), Redline, S. (Susan), Ridker, P. M. (Paul M.), Rosendaal, F. R. (Frits R.), Saaristo, T. E. (Timo E.), Sandhu, M. (Manjinder), Saramies, J. (Jouko), Schneiderman, N. (Neil), Schwarz, P. (Peter), Scott, L. J. (Laura J.), Selvin, E. (Elizabeth), Sever, P. (Peter), Shu, X.-o. (Xiao-ou), Slagboom, P. E. (P. Eline), Small, K. S. (Kerrin S.), Smith, B. H. (Blair H.), Snieder, H. (Harold), Sofer, T. (Tamar), Sorensen, T. I. (Thorkild I. A.), Spector, T. D. (Tim D.), Stanton, A. (Alice), Steves, C. J. (Claire J.), Stumvoll, M. (Michael), Sun, L. (Liang), Tabara, Y. (Yasuharu), Tai, E. S. (E. Shyong), Timpson, N. J. (Nicholas J.), Tonjes, A. (Anke), Tuomilehto, J. (Jaakko), Tusie, T. (Teresa), Uusitupa, M. (Matti), van der Harst, P. (Pim), van Duijn, C. (Cornelia), Vitart, V. (Veronique), Vollenweider, P. (Peter), Vrijkotte, T. G. (Tanja G. M.), Wagenknecht, L. E. (Lynne E.), Walker, M. (Mark), Wang, Y. X. (Ya X.), Wareham, N. J. (Nick J.), Watanabe, R. M. (Richard M.), Watkins, H. (Hugh), Wei, W. B. (Wen B.), Wickremasinghe, A. R. (Ananda R.), Willemsen, G. (Gonneke), Wilson, J. F. (James F.), Wong, T.-Y. (Tien-Yin), Wu, J.-Y. (Jer-Yuarn), Xiang, A. H. (Anny H.), Yanek, L. R. (Lisa R.), Yengo, L. (Loic), Yokota, M. (Mitsuhiro), Zeggini, E. (Eleftheria), Zheng, W. (Wei), Zonderman, A. B. (Alan B.), Rotter, J. I. (Jerome I.), Gloyn, A. L. (Anna L.), McCarthy, M. I. (Mark I.), Dupuis, J. (Josee), Meigs, J. B. (James B.), Scott, R. A. (Robert A.), Prokopenko, I. (Inga), Leong, A. (Aaron), Liu, C.-T. (Ching-Ti), Parker, S. C. (Stephen C. J.), Mohlke, K. L. (Karen L.), Langenberg, C. (Claudia), Wheeler, E. (Eleanor), Morris, A. P. (Andrew P.), Barroso, I. (Ines)

الوصف: Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10-8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.

وصف الملف: application/pdf

العلاقة: info:eu-repo/grantAgreement/EC/H2020/633595/EU/Understanding the dynamic determinants of glucose homeostasis and social capability to promote Healthy and active aging/DYNAHEALTH; info:eu-repo/grantAgreement/EC/H2020/733206/EU/Early-life stressors and LifeCycle health/LIFECYCLE; info:eu-repo/grantAgreement/EC/H2020/825762/EU/Metabolic effects of Endocrine Disrupting Chemicals: novel testing METhods and adverse outcome pathways/EDCMET; info:eu-repo/grantAgreement/EC/H2020/824989/EU/A federated FAIR platform enabling large-scale analysis of high-value cohort data connecting Europe and Canada in personalized health/EUCAN-Connect; info:eu-repo/semantics/altIdentifier/pissn/1061-4036; info:eu-repo/semantics/altIdentifier/eissn/1546-1718

الإتاحة: http://urn.fi/urn:nbn:fi-fe2022030422054Test

المؤلفون: Liu, J. (Jingyu), Chen, J. (Ji), Ehrlich, S.M. (Stefan), Walton, E. (Esther), White, T.J.H. (Tonya), Perrone-Bizzozero, N. (Nora), Bustillo, J., Turner, J. (Jessica), Calhoun, V.D. (Vince)

المصدر: Schizophrenia Bulletin vol. 40 no. 4, pp. 769-776

مصطلحات موضوعية: gene expression, hyper- or hypomethylation, inflammatory response, reality distortion symptom

الوصف: DNA methylation, one of the main epigenetic mechanisms to regulate gene expression, appears to be involved in the development of schizophrenia (SZ). In this study, we investigated 7562 DNA methylation markers in blood from 98 SZ patients and 108 healthy controls. A linear regression model including age, gender, race, alcohol, nicotine and cannabis use status, and diagnosis was implemented to identify C-phosphate-G (CpG) sites significantly associated with diagnosis. These CpG sites were further validated using an independent data set. Sixteen CpG sites were identified with hyper- or hypomethylation in patients. A further verification of expression of the corresponding genes identified 7 genes whose expression levels were also significantly altered in patients. While such altered methylation patterns showed no correlation with disorganized symptoms and negative symptoms in patients, 11 CpG sites significantly correlated with reality distortion symptoms. The direction of the correlations indicates that methylation changes possibly play a protective mechanism to lessen delusion and hallucination symptoms in patients. Pathway analyses showed that the most significant biological function of the differentially methylated CpGs is inflammatory response with CD224, LAX1, TXK, PRF1, CD7, MPG, and MPO genes directly involved in activations of T cells, B cells, and natural killer cells or in cytotoxic reaction. Our results suggest that such methylation changes may modulate aspects of the immune response and hence protect against the neurobiological substrate of reality distortion symptoms in SZ patients.

العلاقة: http://repub.eur.nl/pub/70901Test; urn:hdl:1765/70901

الإتاحة: https://doi.org/10.1093/schbul/sbt080Test
http://repub.eur.nl/pub/70901Test

المؤلفون: Pan, W. (Wei), Jin, Y. (Ying), Chen, J. (Ji), Rottier, R.J. (Robbert), Steel, J. (John), Kiernan, A.E. (Amy)

المصدر: The Journal of Neuroscience vol. 33 no. 41, pp. 16146-16157

الوصف: Hearing impairment or vestibular dysfunction in humans often results from a permanent loss of critical cell types in the sensory regions of the inner ear, including hair cells, supporting cells, or cochleovestibular neurons. These important cell types arise from a common sensory or neurosensory progenitor, although little is known about how these progenitors are specified. Studies have shown that Notch signaling and the transcription factor Sox2 are required for the development of these lineages. Previously we and others demonstrated that ectopic activation of Notch can direct nonsensory cells to adopt a sensory fate, indicating a role for Notch in early specification events. Here, we explore the relationship between Notch and SOX2 by ectopically activating these factors in nonsensory regions of the mouse cochlea, and demonstrate that, similar to Notch, SOX2 can specify sensory progenitors, consistent with a role downstream of Notch signaling. However, we also show that Notch has a unique role in promoting the proliferation of the sensory progenitors. We further demonstrate that Notch can only induce ectopic sensory regions within a certain time window of development, and that the ectopic hair cells display specialized stereocilia bundles similar to endogenous hair cells. These results demonstrate that Notch and SOX2 can both drive the sensory program in nonsensory cells, indicating these factors may be useful in cell replacement strategies in the inner ear.

العلاقة: http://repub.eur.nl/pub/61422Test; urn:hdl:1765/61422

الإتاحة: https://doi.org/10.1523/JNEUROSCI.3150-12.2013Test
http://repub.eur.nl/pub/61422Test

المؤلفون: Li, Z. (Zhixiong), Ribbers, P.M.A. (Piet), Li, Y. (Yuanyuan), Jiang, X. (Xinyi), Chen, P. (Ping), Arnovitz, S. (Stephen), Radmacher, M.D. (Michael), Maharry, K. (Kati), Elkahloun, A.G. (Abdel), Yang, X. (Xinan), He, C. (Chunjiang), He, M. (Meian), Zhang, Z. (Zhiyu), Döhner, K. (Konstanze), Neilly, M.B. (Mary Beth), Price, C. (Colles), Lussier, Y.A. (Yves), Zhang, Y. (Yanming), Larson, R.A. (Richard), Beau, M.M. (Michelle) le, Caligiuri, M.A. (Michael), Bullinger, L. (Lars), Valk, P.J.M. (Peter), Delwel, H.R. (Ruud), Löwenberg, B. (Bob), Liu, P.P. (Paul), Marcucci, G. (Guido), Bloomfield, C.D. (Clara), Rowley, J.D. (Janet), Chen, J. (Ji)

المصدر: Blood vol. 119 no. 10, pp. 2314-2324

العلاقة: http://repub.eur.nl/pub/69612Test; urn:hdl:1765/69612

الإتاحة: https://doi.org/10.1182/blood-2011-10-386235Test
http://repub.eur.nl/pub/69612Test