Evaluation Of Chromatin Accessibility In Prefrontal Cortex Of Schizophrenia Cases And Controls
作者： Julien Bryois , Melanie E Garrett , Lingyun Song , Alexias Safi , Paola Giusti-Rodriguez
DOI: 10.1101/141986
关键词:
摘要: Schizophrenia genome-wide association (GWA) studies have identified over 150 regions of the genome that are associated with disease risk, yet there is little evidence coding mutations contribute to this disorder. To explore mechanism non-coding regulatory elements in schizophrenia, we performed ATAC-seq on adult prefrontal cortex brain samples from 135 individuals schizophrenia and 137 controls, 118,152 peaks. These accessible chromatin highly enriched for SNP-heritability (10.6 fold enrichment, P=2.4x10-4, second only genomic conserved Eutherian mammals) replicated an independent dataset (9.0 P=2.7x10-4). This degree enrichment heritability was higher than open found 138 different cell tissue types. Brain overlapped exhibited even indicating conservation can identify functional subsets within active brain. However, did not accessibility differences between cases nor find interaction QTLs case-control status. indicates although causal variants map elements, mechanisms other differential may govern contribution element variation risk. Our results strongly implicate gene processes involving pathogenesis suggest a strategy understand hundreds common emerging large complex diseases.
sci-hub.st 参考文章(107)
PAUL LICHTENSTEIN, CAMILLA BJÖRK, CHRISTINA M. HULTMAN, EDWARD SCOLNICK, PAMELA SKLAR, PATRICK F. SULLIVAN, Recurrence risks for schizophrenia in a Swedish national cohort. Psychological Medicine. ,vol. 36, pp. 1417- 1425 ,(2006) , 10.1017/S0033291706008385
James J Lee, Shaun M Purcell, Shashaank Vattikuti, Laurent CAM Tellier, Carson C Chow, Christopher C Chang, None, Second-generation PLINK: rising to the challenge of larger and richer datasets GigaScience. ,vol. 4, pp. 7- 7 ,(2015) , 10.1186/S13742-015-0047-8
Jon McClellan, Mary-Claire King, Genetic Heterogeneity in Human Disease Cell. ,vol. 141, pp. 210- 217 ,(2010) , 10.1016/J.CELL.2010.03.032
Gianna Sepede, Domenico De Berardis, Daniela Campanella, Mauro Gianni Perrucci, Antonio Ferretti, Nicola Serroni, Francesco Saverio Moschetta, Cosimo Del Gratta, Rosa Maria Salerno, Filippo Maria Ferro, Massimo Di Giannantonio, Marco Onofrj, Gian Luca Romani, Francesco Gambi, Impaired sustained attention in euthymic bipolar disorder patients and non-affected relatives: an fMRI study Bipolar Disorders. ,vol. 14, pp. 764- 779 ,(2012) , 10.1111/BDI.12007
Christos Pantelis, George N Papadimitriou, Sergi Papiol, Elena Parkhomenko, Michele T Pato, Tiina Paunio, Milica Pejovic-Milovancevic, Diana O Perkins, Olli Pietiläinen, Jonathan Pimm, Andrew J Pocklington, John Powell, Alkes Price, Ann E Pulver, Shaun M Purcell, Digby Quested, Henrik B Rasmussen, Abraham Reichenberg, Mark A Reimers, Alexander L Richards, Joshua L Roffman, Panos Roussos, Douglas M Ruderfer, Veikko Salomaa, Alan R Sanders, Ulrich Schall, Christian R Schubert, Thomas G Schulze, Sibylle G Schwab, Edward M Scolnick, Rodney J Scott, Larry J Seidman, Jianxin Shi, Engilbert Sigurdsson, Teimuraz Silagadze, Jeremy M Silverman, Kang Sim, Petr Slominsky, Jordan W Smoller, Hon-Cheong So, ChrisC A Spencer, Eli A Stahl, Hreinn Stefansson, Stacy Steinberg, Elisabeth Stogmann, Richard E Straub, Eric Strengman, Jana Strohmaier, T Scott Stroup, Mythily Subramaniam, Jaana Suvisaari, Dragan M Svrakic, Jin P Szatkiewicz, Erik Söderman, Srinivas Thirumalai, Draga Toncheva, Sarah Tosato, Juha Veijola, John Waddington, Dermot Walsh, Dai Wang, Qiang Wang, Bradley T Webb, Mark Weiser, Dieter B Wildenauer, Nigel M Williams, Stephanie Williams, Stephanie H Witt, Aaron R Wolen, Emily HM Wong, Brandon K Wormley, Hualin Simon Xi, Clement C Zai, Xuebin Zheng, Fritz Zimprich, Naomi R Wray, Kari Stefansson, Peter M Visscher, Wellcome Trust Case-Control Consortium, Rolf Adolfsson, Ole A Andreassen, Douglas HR Blackwood, Elvira Bramon, Joseph D Buxbaum, Anders D Børglum, Sven Cichon, Ariel Darvasi, Enrico Domenici, Hannelore Ehrenreich, Tõnu Esko, Pablo V Gejman, Michael Gill, Hugh Gurling, Christina M Hultman, Nakao Iwata, Assen V Jablensky, Erik G Jönsson, Kenneth S Kendler, George Kirov, Jo Knight, Todd Lencz, Douglas F Levinson, Qingqin S Li, Jianjun Liu, Anil K Malhotra, Steven A McCarroll, Andrew McQuillin, Jennifer L Moran, Preben B Mortensen, Bryan J Mowry, Markus M Nöthen, Roel A Ophoff, Michael J Owen, Aarno Palotie, Carlos N Pato, Tracey L Petryshen, Danielle Posthuma, Marcella Rietschel, Brien P Riley, Dan Rujescu, Pak C Sham, Pamela Sklar, David St Clair, Daniel R Weinberger, Jens R Wendland, Thomas Werge, Mark J Daly, Patrick F Sullivan, Michael C O’Donovan, None, Biological insights from 108 schizophrenia-associated genetic loci Nature. ,vol. 511, pp. 421- 427 ,(2014) , 10.1038/NATURE13595
Dan Rujescu, Andres Ingason, Sven Cichon, Olli P.H. Pietiläinen, Michael R. Barnes, Timothea Toulopoulou, Marco Picchioni, Evangelos Vassos, Ulrich Ettinger, Elvira Bramon, Robin Murray, Mirella Ruggeri, Sarah Tosato, Chiara Bonetto, Stacy Steinberg, Engilbert Sigurdsson, Thordur Sigmundsson, Hannes Petursson, Arnaldur Gylfason, Pall I. Olason, Gudmundur Hardarsson, Gudrun A. Jonsdottir, Omar Gustafsson, Ragnheidur Fossdal, Ina Giegling, Hans-Jürgen Möller, Annette M. Hartmann, Per Hoffmann, Caroline Crombie, Gillian Fraser, Nicholas Walker, Jouko Lonnqvist, Jaana Suvisaari, Annamari Tuulio-Henriksson, Srdjan Djurovic, Ingrid Melle, Ole A. Andreassen, Thomas Hansen, Thomas Werge, Lambertus A. Kiemeney, Barbara Franke, Joris Veltman, Jacobine E. Buizer-Voskamp, Chiara Sabatti, Roel A. Ophoff, Marcella Rietschel, Markus M. Nöthen, Kari Stefansson, Leena Peltonen, David St Clair, Hreinn Stefansson, David A. Collier, , Disruption of the neurexin 1 gene is associated with schizophrenia Human Molecular Genetics. ,vol. 18, pp. 988- 996 ,(2009) , 10.1093/HMG/DDN351
Mark D Robinson, Alicia Oshlack, A scaling normalization method for differential expression analysis of RNA-seq data Genome Biology. ,vol. 11, pp. 1- 9 ,(2010) , 10.1186/GB-2010-11-3-R25
Nick Patterson, Alkes L. Price, David Reich, Population structure and eigenanalysis PLOS Genetics. ,vol. 2, pp. 2074- 2093 ,(2006) , 10.1371/JOURNAL.PGEN.0020190
H. Li, B. Handsaker, A. Wysoker, T. Fennell, J. Ruan, N. Homer, G. Marth, G. Abecasis, R. Durbin, , The Sequence Alignment/Map format and SAMtools Bioinformatics. ,vol. 25, pp. 2078- 2079 ,(2009) , 10.1093/BIOINFORMATICS/BTP352
Stef van Buuren, Karin Groothuis-Oudshoorn, mice: Multivariate Imputation by Chained Equations inR Journal of Statistical Software. ,vol. 45, pp. 1- 67 ,(2011) , 10.18637/JSS.V045.I03