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ūüďį Genome sequencing unveils a regulatory landscape of platelet reactivity | Nature Communications

Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Ali R. Keramati & Lewis C. Becker

GeneSTAR Research Program, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Ali R. Keramati, Lisa R. Yanek, Nauder Faraday, Lewis C. Becker & Rasika A. Mathias

Division of Intramural Research, Population Sciences Branch, National Heart, Lung and Blood Institute, Bethesda, MD, USA

Ming-Huei Chen, Benjamin A. T. Rodriguez & Andrew D. Johnson

The Framingham Heart Study, Framingham, MA, USA

Ming-Huei Chen, Benjamin A. T. Rodriguez, Achilleas N. Pitsillides, L. Adrienne Cupples & Andrew D. Johnson

Valo Health, Boston, MA, USA

Benjamin A. T. Rodriguez

Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Lisa R. Yanek

Boston Children's Hospital, Boston, MA, USA

Arunoday Bhan & Thorsten M. Schlaeger

Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA

Brady J. Gaynor, Kathleen Ryan, Jeffrey R. O'Connell, Braxton D. Mitchell & Joshua P. Lewis

Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Baltimore, MD, USA

Brady J. Gaynor, Kathleen Ryan, Alan R. Shuldiner, Jeffrey R. O'Connell, Braxton D. Mitchell & Joshua P. Lewis

Cardiovascular Health Research Unit, University of Washington School of Medicine, Seattle, WA, USA

Jennifer A. Brody

Vanderbilt Genetics Institute, Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

Xue Zhong

Vanderbilt Genetics Institute, Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA

Qiang Wei & Bingshan Li

Biostatistics and Bioinformatics, Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Kai Kammers

Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Kanika Kanchan, Kruthika Iyer & Rasika A. Mathias

Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA

Madeline H. Kowalski

Department of Biostatistics, School of Public Health, Boston University, Boston, MA, USA

Achilleas N. Pitsillides & L. Adrienne Cupples

Bloomberg School of Public Health, Biostatistics, Johns Hopkins University, Baltimore, MD, USA

Ingo Ruczinski & Margaret A. Taub

Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Nauder Faraday

New York Genome Center, New York, NY, USA

Namiko Abe, Karen Bunting, Bo-Juen Chen, Heather Geiger, Soren Germer, Melissa Marton, Catherine Reeves, Nicolas Robine, Alexi Runnels, Tanja Smith, Lara Winterkorn & Michael Zody

University of Michigan, Ann Arbor, MI, USA

Goncalo Abecasis, Larry Bielak, Thomas Blackwell, Jeffrey Curtis, Matthew Flickinger, Colin Gross, Hyun Min Kang, Sharon Kardia, Jonathon LeFaive, Patricia Peyser, Jacob Pleiness, Albert Vernon Smith, Jennifer Smith, Daniel Taliun, Peter VandeHaar, Jiongming Wang, Cristen Willer, Ketian Yu, Wei Zhao & Sebastian Zoellner

Broad Institute, Cambridge, MA, USA

Francois Aguet, Kristin Ardlie, Mark Chaffin, Seung Hoan Choi, Clary Clish, Stacey Gabriel, Namrata Gupta, Pradeep Natarajan, Carolina Roselli & Seyedeh Maryam Zekavat

Cedars Sinai, Boston, MA, USA

Christine Albert

Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, USA

Laura Almasy

Emory University, Atlanta, GA, USA

Alvaro Alonso, Rich Johnston, Lawrence S. Phillips, Zhaohui Qin, Vivien Sheehan & Stephanie L. Sherman

University of Maryland, Baltimore, MD, USA

Seth Ament, Amber Beitelshees, Christy Chang, Coleen Damcott, Scott Devine, Mao Fu, Da-Wei Gong, Yue Guan, Elliott Hong, Michael Kessler, Joshua Lewis, Patrick McArdle, Braxton D. Mitchell, May E. Montasser, Tim O'Connor, James Perry, Toni Pollin, Robert Reed, Kathleen Ryan, Shabnam Salimi, Amol Shetty, Elizabeth Streeten, Simeon Taylor & Huichun Xu

University of Washington, Seattle, WA, USA

Peter Anderson, Joshua Bis, Jennifer Brody, Jai Broome, Erin Buth, Matthew Conomos, Colleen Davis, Leslie Emery, Chris Frazar, Stephanie M. Fullerton, Stephanie Gogarten, Ben Heavner, Susan Heckbert, Deepti Jain, Craig Johnson, Alyna Khan, Cathy Laurie, Cecelia Laurie, David Levine, Susanne May, Daniel McGoldrick, Caitlin McHugh, Sarah C. Nelson, Deborah Nickerson, Bruce Psaty, Ken Rice, Josh Smith, Nicholas Smith, Nona Sotoodehnia, Adrienne M. Stilp, Adam Szpiro, Timothy A. Thornton, Machiko Threlkeld, David Tirschwell, Catherine Tong, Fei Fei Wang, Bruce Weir, Kayleen Williams & Quenna Wong

University of Mississippi, Jackson, MS, USA

Pramod Anugu, Adolfo Correa, Lynette Ekunwe, Yan Gao, Michael Hall, Hao Mei & Nancy Min

National Institutes of Health, Bethesda, MD, USA

Deborah Applebaum-Bowden

Johns Hopkins University, Baltimore, MD, USA

Dan Arking, Dimitrios Avramopoulos, Emily Barron-Casella, Terri Beaty, Diane Becker, Lewis Becker, James Casella, Kimberly Jones, Barry Make, Rasika Mathias, Rakhi Naik, Wendy Post, Ingo Ruczinski, Steven Salzberg, Margaret Taub, Dhananjay Vaidya & Lisa Yanek

University of Kentucky, Lexington, KY, USA

Donna K. Arnett

Duke University, Durham, NC, USA

Allison Ashley-Koch, Yongmei Liu & Marilyn Telen

University of Alabama, Birmingham, LA, USA

Stella Aslibekyan, Bertha Hidalgo, Marguerite Ryan Irvin, Merry-Lynn McDonald & Hemant Tiwari

Stanford University, Stanford, CA, USA

Tim Assimes, Carlos Bustamante, Chris Gignoux, Yu Liu, David T. Paik, Marco Perez, Michael Snyder, Hua Tang & Joseph Wu

University of Wisconsin Milwaukee, Milwaukee, WI, USA

Paul Auer

Providence Health Care, Vancouver, BC, Canada

Najib Ayas

Baylor College of Medicine Human Genome Sequencing Center, Houston, TX, USA

Adithya Balasubramanian, Huyen Dinh, Harsha Doddapaneni, Shannon Dugan-Perez, Jesse Farek, Richard Gibbs, Yi Han, Jianhong Hu, Ziad Khan, Sandra Lee, Vipin Menon, Ginger Metcalf, Zeineen Momin, Donna Muzny, Caitlin Nessner, Osuji Nkechinyere, Geoffrey Okwuonu, Mahitha Rajendran, Sejal Salvi, Jireh Santibanez & Jennifer Watt

Cleveland Clinic, Cleveland, OH, USA

John Barnard, Gerald Beck, Mina Chung, Suzy Comhair & Serpil Erzurum

University of Colorado Anschutz Medical Campus, Aurora, OH, USA

Kathleen Barnes, Sharon Graw, Luisa Mestroni & Matthew Taylor

Columbia University, New York, NY, USA

R. Graham Barr & Danish Saleheen

The Emmes Corporation, Rockville, MD, USA

Lucas Barwick

National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA

Rebecca Beer, Weiniu Gan, Cashell Jaquish, Andrew Johnson, Dan Levy, James Luo, Julie Mikulla, George Papanicolaou & Pankaj Qasba

Boston University, Massachusetts General Hospital, Boston, MA, USA

Emelia Benjamin

University of Pittsburgh, Pittsburgh, PA, USA

Takis Benos, Mark Geraci, Mark Gladwin, Ryan L. Minster, Frank Sciurba, Daniel E. Weeks & Yingze Zhang

Fundação de Hematologia e Hemoterapia de Pernambuco - Hemope, Recife, BR, Brazil

Marcos Bezerra

University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA

John Blangero, Joanne Curran & Michael Mahaney

University of Texas Health at Houston, Houston, TX, USA

Eric Boerwinkle, Deborah Brown, Paul de Vries, Myriam Fornage & James Hixson

Wake Forest Baptist Health, Winston-Salem, MA, USA

Donald W. Bowden, David Herrington, Nicholette Palmer & Beverly Snively

National Jewish Health, Denver, CO, USA

Russell Bowler, James Crapo, Tasha Fingerlin, Elizabeth Regan & Snow Xueyan Zhao

Medical College of Wisconsin, Milwaukee, WI, USA

Ulrich Broeckel

University of California, San Francisco, San Francisco, CA, USA

Esteban Burchard, Ryan Hernandez & Shannon Kelly

Brigham & Women's Hospital, Boston, MA, USA

Brian Cade, Vincent Carey, Juan P. Casas Romero, Peter Castaldi, Daniel Chasman, Michael Cho, Dawn DeMeo, Auyon Ghosh, Craig Hersh, Brian Hobbs, Meryl LeBoff, Jiwon Lee, JoAnn Manson, Matt Moll, Dandi Qiao, Susan Redline, Edwin Silverman, Tamar Sofer, Jessica Lasky Su, Jody Sylvia, Scott T. Weiss & Carla Wilson

University of Colorado at Denver, Denver, CO, USA

Jonathan Cardwell, Sameer Chavan, Michelle Daya, Shanshan Gao, Daniel Grine, John Hokanson, Ethan Lange, Leslie Lange, Susan Mathai, Bonnie Neltner, Julia Powers Becker, Meher Preethi Boorgula, Nicholas Rafaels, Pamela Russell, David Schwartz, Aniket Shetty, Garrett Storm, Tarik Walker, Avram Walts & Ivana Yang

University of Montreal, Montreal, QC, Canada

Julie Carrier

Washington State University, Pullman, WA, USA

Cara Carty

University of California, Los Angeles, Los Angeles, CA, USA

Richard Casaburi, Carolyn Crandall & Karol Watson

National Taiwan University, Taipei, TW, Taiwan

Yi-Cheng Chang & Lee-Ming Chuang

University of Virginia, Charlottesville, VA, USA

Wei-Min Chen, Charles Farber & Josyf C. Mychaleckyj

Lundquist Institute, Torrance, CA, USA

Yii-DerIda Chen, Xiuqing Guo, Henry Lin, Ani Manichaikul, Aakrosh Ratan, Stephen Rich, Jerome Rotter, Kevin Sandow & Kent D. Taylor

National Health Research Institute Taiwan, Miaoli County, TW, Taiwan

Ren-Hua Chung & Chao Agnes Hsiung

University of Vermont, Burlington, VT, USA

Elaine Cornell, Jon Peter Durda & Russell Tracy

Boston University, Boston, MA, USA

L. Adrienne Cupples, Honghuang Lin, Kathryn Lunetta & Gina Peloso

Vitalant Research Institute, San Francisco, CA, USA

Brian Custer & Vasan S. Ramachandran

University of Illinois at Chicago, Chicago, IL, USA

Dawood Darbar

University of Chicago, Chicago, IL, USA

Sean David

Mayo Clinic, Rochester, NY, USA

Mariza de Andrade

Washington University in St Louis, St. Louis, WA, USA

Lisa de las Fuentes, Susan K. Dutcher, Lucinda Fulton, C.Charles Gu, D. C. Rao & Karen Schwander

Vanderbilt University, Nashville, TN, USA

Michael DeBaun, Dan Roden, M. Benjamin Shoemaker & Yun Ju Sung

University of Cincinnati, Cincinnati, OH, USA

Ranjan Deka

University of North Carolina, Chapel Hill, NC, USA

Qing Duan, Nora Franceschini, Yun Li, Kari North, Juan Manuel Peralta & Laura Raffield

University of Texas Rio Grande Valley School of Medicine, Edinburg, TX, USA

Ravi Duggirala

Brown University, Providence, RI, USA

Charles Eaton, Simin Liu & Stephen McGarvey

Harvard University, Cambridge, MA, USA

Adel El Boueiz, Wonji Kim, Steven Lubitz, Sean McFarland, James Meigs, Vijay G. Sankaran & Lu-Chen Weng

Massachusetts General Hospital, Boston, MA, USA

Patrick Ellinor, Ulrike Peters & Lesley Tinker

Fred Hutchinson Cancer Research Center, Seattle, WA, USA

Margery Gass

Icahn School of Medicine at Mount Sinai, New York, NY, USA

Bruce Gelb, Jeff Haessler, Eimear Kenny, Charles Kooperberg, Ruth J. F. Loos & Michael Preuss

Beth Israel Deaconess Medical Center, Boston, MA, USA

Robert Gerszten & Girish Nadkarni

Boston Children's Hospital, Harvard Medical School, Boston, MA, USA

David Glahn

University of Texas Rio Grande Valley School of Medicine, San Antonio, TX, USA

Harald Goring

Mass General Brigham, Boston, MA, USA

Kathryn J. Gray

Indiana University, Indianapolis, IN, USA

David M. Haas & Jennifer Wessel

University of Calgary, Calgary, AB, Canada

Patrick Hanly

University of Maryland, Philadelphia, PA, USA

Daniel Harris

Yale University, New Haven, CT, USA

Nicola L. Hawley

Tulane University, New Orleans, LA, USA

Jiang He

University of Iowa, Iowa City, IA, USA

Karin Hoth & Robert Wallace

Tri-Service General Hospital National Defense Medical Center, Taichung City, TW, Taiwan

Yi-Jen Hung

Blood Works Northwest, Seattle, WA, USA

Haley Huston, Jill Johnsen, Barbara Konkle & Sarah Ruuska

Taichung Veterans General Hospital Taiwan, Taichung City, TW, Taiwan

Chii Min Hwu, Wen-Jane Lee, Xiaohui Li & Wayne Hui-Heng Sheu

Oklahoma State University Medical Center, Columbus, OK, USA

Rebecca Jackson

Albert Einstein College of Medicine, New York, NY, USA

Robert Kaplan & Sylvia Smoller

McGill University, Montréal, Quebec, CA, USA

John Kimoff

Harvard School of Public Health, Boston, MA, USA

Christoph Lange & Xihong Lin

University of Colorado at Denver, Aurora, CO, USA

Greg Kinney

Loyola University, Maywood, IL, USA

Holly Kramer

Ohio State University, Columbus, OH, USA

Ulysses Magalang

Broad Institute, Harvard University, Massachusetts General Hospital, Cambridge, MA, USA

Alisa Manning

George Washington University, Washington, WA, USA

Lisa Martin

RTI International, Washington, WA, USA

Becky McNeil

University of Arizona, Tucson, AZ, USA

Deborah A. Meyers

Stanford University, Palo Alto, CA, USA

Emmanuel Mignot

National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA

Mollie Minear

Oklahoma Medical Research Foundation, Oklahoma City, OK, USA

Courtney Montgomery

Ministry of Health, Government of Samoa, Apia, WS, Samoa

Take Naseri

Howard University, Washington, WA, USA

Sergei Nekhai

University of Maryland, Balitmore, MD, USA

Jeff O'Connell

University at Buffalo, Buffalo, NY, USA

Heather Ochs-Balcom

University of Pennsylvania, Philadelphia, PA, USA

Allan Pack & Sarah Tishkoff

University of Minnesota, Minneapolis, MN, USA

James Pankow, Michael Tsai & Scott Vrieze

RTI International, Research Triangle Park, NC, USA

Cora Parker

Northwestern University, Chicago, IL, USA

Laura Rasmussen-Torvik

Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, USA

Alex Reiner

Lutia I Puava Ae Mapu I Fagalele, Apia, WS, Samoa

Muagututi'a Sefuiva Reupena

University of Ottawa, Ottawa, QC, Canada

Rebecca Robillard

Universidade de Sao Paulo, Sao Paulo, BR, Brazil

Ester Cerdeira Sabino

Harvard Medical School, Boston, MA, USA

Christine Seidman & Jonathan Seidman

Université Laval, Quebec City, CA, USA

Frederic Series

UMass Memorial Medical Center, Worcester, MA, USA

Brian Silver

University of Saskatchewan, Saskatoon, SK, Canada

Robert Skomro

University of Southern California, Los Angeles, CA, USA

David Van Den Berg

Brigham & Women's Hospital, Mass General Brigham, Boston, MA, USA

Heming Wang

Henry Ford Health System, Detroit, MI, USA

L. Keoki Williams

Beth Israel Deaconess Medical Center, Cambridge, MA, USA

James Wilson

Case Western Reserve University, Cleveland, OH, USA

Xiaofeng Zhu

A.R.K., M.-H.C., B.A.T.R. led equal roles in analysis, interpretation and writing of the paper. J.P.L., R.A.M., A.D.J. led equal senior roles for the study. A.R.K. wrote the first draft of manuscript with contribution and editing from M.-H.C., B.A.T.R., L.R.Y., M.A.T., J.A.B., L.C.B., N.F., J.P.L., R.A.M. and A.D.J. Genome wide analyses were performed by A.R.K., B.A.T.R., B.J.G., L.R.Y., M.-H.C. and K.R. RNA-sequencing and eQTL analyses were performed by R.A.M., Kai.K., M.A.T., I.R., L.R.Y., A.R.K., Kan.K. and K.I. Imputation of genomic data and replication analyses were performed by M.-H.C., B.A.T.R., L.R.Y., B.J.G., A.P., L.A.C., and M.H.K. L.R.Y., N.F., L.C.B. and R.A.M. were involved in the guidance, collection and analysis for Genetic Study of Atherosclerosis Risk (GeneSTAR) phenotype data. B.J.G., K.R., B.D.M., J.P.L., J.R.O. and A.R.S. were involved in the guidance, collection and analysis for Older Order Amish Study (OAA) phenotype data. B.A.T.R., M.-H.C. and A.D.J. were involved in the guidance and analysis for Framingham Heart Study (FHS) phenotype data. T.M.S. and A.B. established the imMKCL system, and A.B. designed all functional experiments with input from B.A.T.R. and A.D.J. and carried them out. X.Z., Q.W. and B.L. carried out BioVU pheWAS analyses. A.D.J. funded genotyping of the CaPS cohort. M.-H.C. performed genotype QC, calling and imputation of the CaPS cohort with input from A.D.J., B.A.T.R., M.-H.C. and A.D.J. conducted CaPS genotype-phenotype analyses.

 
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