Large eQTL meta-analysis reveals differing patterns between cerebral cortical and cerebellar brain regions
Solveig K. Sieberts(Sage Bionetworks), Thanneer M. Perumal(Sage Bionetworks), Minerva M. Carrasquillo(Mayo Clinic in Florida), Mariet Allen(Mayo Clinic in Florida), Joseph S. Reddy(Mayo Clinic in Florida), Gabriel E. Hoffman(Icahn School of Medicine at Mount Sinai), Kristen K. Dang(Sage Bionetworks), John Calley(Eli Lilly (United States)), Philip J. Ebert(Eli Lilly (United States)), James A. Eddy(Sage Bionetworks), Xue Wang(Mayo Clinic in Florida), Anna K. Greenwood(Sage Bionetworks), Sara Mostafavi(Canadian Institute for Advanced Research), Schahram Akbarian(Icahn School of Medicine at Mount Sinai), Jaroslav Bendl(Icahn School of Medicine at Mount Sinai), Michael S. Breen(Icahn School of Medicine at Mount Sinai), Kristen Brennand(Icahn School of Medicine at Mount Sinai), Leanne Brown(Icahn School of Medicine at Mount Sinai), Andrew Browne(Allen Institute for Brain Science), Joseph D. Buxbaum(Allen Institute for Brain Science), Alexander W. Charney(Icahn School of Medicine at Mount Sinai), Andrew Chess(Icahn School of Medicine at Mount Sinai), Lizette Couto(Icahn School of Medicine at Mount Sinai), Greg Crawford(Duke University), Olivia Devillers(Icahn School of Medicine at Mount Sinai), Bernie Devlin(University of Pittsburgh), Amanda Dobbyn(Icahn School of Medicine at Mount Sinai), Enrico Domenici(University of Trento), Michele Filosi(University of Trento), Elie Flatow(Icahn School of Medicine at Mount Sinai), Nancy Francoeur(Icahn School of Medicine at Mount Sinai), John F. Fullard(Icahn School of Medicine at Mount Sinai), Sergio Espeso‐Gil(Icahn School of Medicine at Mount Sinai), Kiran Girdhar(Icahn School of Medicine at Mount Sinai), Attila Gulyás-Kovács(Icahn School of Medicine at Mount Sinai), Raquel E. Gur(University of Pennsylvania), Chang-Gyu Hahn(University of Pennsylvania), Vahram Haroutunian(Icahn School of Medicine at Mount Sinai), Mads E. Hauberg(Aarhus University), Laura M. Huckins(Icahn School of Medicine at Mount Sinai), Rivky Jacobov(Icahn School of Medicine at Mount Sinai), Yan Jiang(Icahn School of Medicine at Mount Sinai), Jessica Johnson(Icahn School of Medicine at Mount Sinai), Bibi Kassim(Icahn School of Medicine at Mount Sinai), Yungil Kim(Icahn School of Medicine at Mount Sinai), Lambertus Klei(University of Pittsburgh), Robin S. S. Kramer(National Institutes of Health), Mario Lauria(University of Trento), Thomas Lehner(National Institute of Mental Health), David A. Lewis(University of Pittsburgh), Barbara K. Lipska(National Institutes of Health), Kelsey S. Montgomery(Sage Bionetworks), Royce Park(Icahn School of Medicine at Mount Sinai), Chaggai Rosenbluh(Icahn School of Medicine at Mount Sinai), Panagiotis Roussos(Allen Institute for Brain Science), Douglas M. Ruderfer(Vanderbilt University Medical Center), Geetha Senthil(National Institute of Mental Health), Hardik Shah(Allen Institute for Brain Science), Laura Sloofman(Icahn School of Medicine at Mount Sinai), Lingyun Song(Duke University), Eli Stahl(Icahn School of Medicine at Mount Sinai), Patrick Sullivan(University of North Carolina at Chapel Hill), Roberto Visintainer(University of Trento), Jiebiao Wang(University of Pittsburgh), Ying‐Chih Wang(Eli Lilly (United States)), Jennifer Wiseman(Icahn School of Medicine at Mount Sinai), Eva Xia(Icahn School of Medicine at Mount Sinai), Wen Zhang(Eli Lilly (United States)), Elizabeth Zharovsky(Icahn School of Medicine at Mount Sinai), Laura Addis(Eli Lilly (United States)), Sadiya N. Addo(AbbVie (United States)), David Airey(Eli Lilly (United States)), Matthias Arnold(Helmholtz Zentrum München), David A. Bennett(Rush University Medical Center), Yingtao Bi(AbbVie (United States)), Knut Biber(AbbVie (United States)), Colette Blach(Duke University), Elizabeth Bradhsaw(Columbia University Irving Medical Center), Paul E. Brennan(Nuffield Orthopaedic Centre), Rosa Canet-Aviles(Foundation for the National Institutes of Health), Sherry Cao(AbbVie (United States)), Anna Cavalla(Eli Lilly (United States)), Yooree Chae(Sage Bionetworks), William W. Chen(Biogen (United States)), Jie Cheng(AbbVie (United States)), David Collier(Eli Lilly (United States)), Jeffrey L. Dage(Eli Lilly (United States)), Eric B. Dammer(Emory University), J. Wade Davis(Nuffield Orthopaedic Centre), John B. Davis(Nuffield Orthopaedic Centre), Derek Drake(Harvard University), Duc M. Duong(Emory University), Brian J. Eastwood(Eli Lilly (United States)), Michelle E. Ehrlich(Icahn School of Medicine at Mount Sinai), Benjamin M. Ellingson(AbbVie (United States)), Brett W. Engelmann(AbbVie (United States)), Sahar Esmaeeli-Nieh(AbbVie (United States)), Daniel Felsky(Columbia University Irving Medical Center), Cory C. Funk(Institute for Systems Biology), Chris Gaiteri(Rush University Medical Center), Sam Gandy(Icahn School of Medicine at Mount Sinai), Fan Gao(Massachusetts Institute of Technology), O. Gileadi(Nuffield Orthopaedic Centre), Todd E. Golde(University of Florida), Shaun Grosskurth(AbbVie (United States)), Rishi R. Gupta(AbbVie (United States)), Alex Gutteridge(GlaxoSmithKline (United Kingdom)), Vahram Haroutunian(Icahn School of Medicine at Mount Sinai), Basavaraj Hooli(Eli Lilly (United States)), Neil Humphryes-Kirilov(Eli Lilly (United States)), Koichi Iijima(National Center for Geriatrics and Gerontology), Corey James(Eli Lilly (United States)), Paul Jung(AbbVie (United States)), Rima Kaddurah‐Daouk(Duke University), Gabi Kastenmüller(Helmholtz Zentrum München), Hans‐Ulrich Klein(Columbia University Irving Medical Center), Markus P. Kummer(AbbVie (United States)), Pascale N. Lacor(Eli Lilly (United States)), James J. Lah(Emory University), Emma Laing(Eli Lilly (United States)), Allan I. Levey(Emory University), Yupeng Li(Eli Lilly (United States)), Samantha Lipsky(AbbVie (United States)), Yushi Liu(Eli Lilly (United States)), Jimmy Liu(Biogen (United States)), Zhandong Liu(Baylor College of Medicine), Gregory Louie(Duke University), Tao Lu(Harvard University), Yiyi Ma(Columbia University Irving Medical Center), Yasuji Y. Matsuoka(GlaxoSmithKline (United Kingdom)), Vilas Menon(Columbia University Irving Medical Center), Bradley B. Miller(Eli Lilly (United States)), Thomas P. Misko(AbbVie (United States)), J Mollon(AbbVie (United States)), Kelsey S. Montgomery(Sage Bionetworks), Sumit Mukherjee(Sage Bionetworks), Scott Noggle(New York Stem Cell Foundation), Ping‐Chieh Pao(Massachusetts Institute of Technology), Tracy Young Pearce(Brigham and Women's Hospital), Neil Pearson(Eli Lilly (United States)), Michelle A. Penny(Biogen (United States)), Vladislav Petyuk(Pacific Northwest National Laboratory), Nathan D. Price(Institute for Systems Biology), Danjuma Quarless(AbbVie (United States)), Brinda Ravikumar(AbbVie (United States)), Janina S. Ried(AbbVie (United States)), Cara Ruble(Eli Lilly (United States)), Heiko Runz(Biogen (United States)), Andrew J. Saykin(Indiana University School of Medicine), Eric E. Schadt(Icahn School of Medicine at Mount Sinai), James Scherschel(Eli Lilly (United States)), Nicholas T. Seyfried(Emory University), Joshua Shulman(Baylor College of Medicine), Phil Snyder(Sage Bionetworks), Holly Soares(AbbVie (United States)), Gyan Srivastava(AbbVie (United States)), Henning Stöckmann(AbbVie (United States)), Mariko Taga(Columbia University Irving Medical Center), Shinya Tasaki(Rush University Medical Center), Jessie Tenenbaum(Duke University), Li‐Huei Tsai(Massachusetts Institute of Technology), Aparna Vasanthakumar(AbbVie (United States)), Astrid Wachter(AbbVie (United States)), Yaming Wang(Eli Lilly (United States)), Hong Wang(Eli Lilly (United States)), Minghui Wang(Icahn School of Medicine at Mount Sinai), Christopher D. Whelan(Biogen (United States)), Charles C. White(Broad Institute), Kara Woo(Sage Bionetworks), Paul Wren(GlaxoSmithKline (United Kingdom)), Jessica Wu(AbbVie (United States)), Hualin Simon Xi(AbbVie (United States)), Bruce A. Yankner(Harvard University), Steven G. Younkin(Mayo Clinic in Florida), Lei Yu(Rush University Medical Center), Maria I. Zavodszky(Biogen (United States)), Wenling Zhang(Eli Lilly (United States)), Guoqiang Zhang(Biogen (United States)), Bin Zhang(Icahn School of Medicine at Mount Sinai), Jun Zhu(Icahn School of Medicine at Mount Sinai), Larsson Omberg(Sage Bionetworks), Mette A. Peters(Sage Bionetworks), Benjamin A. Logsdon(Sage Bionetworks), Philip L. De Jager(Columbia University Irving Medical Center), Nilüfer Ertekin‐Taner(Mayo Clinic in Florida), Lara M. Mangravite(Sage Bionetworks)
Cited by 329Open Access
Abstract
The availability of high-quality RNA-sequencing and genotyping data of post-mortem brain collections from consortia such as CommonMind Consortium (CMC) and the Accelerating Medicines Partnership for Alzheimer's Disease (AMP-AD) Consortium enable the generation of a large-scale brain cis-eQTL meta-analysis. Here we generate cerebral cortical eQTL from 1433 samples available from four cohorts (identifying >4.1 million significant eQTL for >18,000 genes), as well as cerebellar eQTL from 261 samples (identifying 874,836 significant eQTL for >10,000 genes). We find substantially improved power in the meta-analysis over individual cohort analyses, particularly in comparison to the Genotype-Tissue Expression (GTEx) Project eQTL. Additionally, we observed differences in eQTL patterns between cerebral and cerebellar brain regions. We provide these brain eQTL as a resource for use by the research community. As a proof of principle for their utility, we apply a colocalization analysis to identify genes underlying the GWAS association peaks for schizophrenia and identify a potentially novel gene colocalization with lncRNA RP11-677M14.2 (posterior probability of colocalization 0.975).
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