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The PAGE Study: How Genetic Diversity Improves Our Understanding of the Architecture of Complex Traits
View ORCID ProfileGenevieve L Wojcik, Mariaelisa Graff, Katherine K Nishimura, Ran Tao, Jeffrey Haessler, Christopher R Gignoux, Heather M Highland, Yesha M Patel, Elena P Sorokin, Christy L Avery, Gillian M Belbin, Stephanie A Bien, Iona Cheng, Sinead Cullina, Chani J Hodonsky, Yao Hu, Laura M Huckins, Janina Jeff, Anne E Justice, Jonathan M Kocarnik, Unhee Lim, Bridget M Lin, Yingchang Lu, Sarah C Nelson, Sung-Shim L Park, Hannah Poisner, Michael H Preuss, Melissa A Richard, Claudia Schurmann, Veronica W Setiawan, Alexandra Sockell, Karan Vahi, Abhishek Vishnu, Marie Verbanck, Ryan Walker, Kristin L Young, Niha Zubair, Victor Acuna-Alonso, Jose Luis Ambite, Kathleen C Barnes, Eric Boerwinkle, Erwin Bottinger, Carlos D Bustamante, Christian Caberto, Samuel Canizales-Quinteroes, Matthew P Conomos, Ewa Deelman, Ron Do, Kimberly Doheny, Lindsay Fernandez-Rhodes, Myriam Fornage, Gerardo Heiss, Brenna Henn, Lucia A Hindorff, Rebecca D Jackson, Benyam Hailu, Cecelia A Laurie, Cathy C Laurie, Yuqing Li, Dan-Yu Lin, Andres Moreno-Estrada, Girish Nadkarni, Paul Norman, Loreall C Pooler, Alexander P Reiner, Jane Romm, Chiara Sabati, Karla Sandoval, Xin Sheng, Eli A Stahl, Daniel O Stram, Timothy A Thornton, Christina L Wassel, Lynne R Wilkens, Cheryl A Winkler, Sachi Yoneyama, Steven Buyske, Chris Haiman, Charles Kooperberg, Loic Le Marchand, Ruth JF Loos, Tara C Matise, Kari E North, Ulrike Peters, Eimear E Kenny, Christopher S Carlson
doi: https://doi.org/10.1101/188094
Genevieve L Wojcik
Stanford University, Stanford CA
Mariaelisa Graff
University of North Carolina at Chapel Hill, Chapel Hill NC
Katherine K Nishimura
Fred Hutchinson Cancer Research Center, Seattle WA
Ran Tao
Vanderbilt University Medical Center, Nashville TN
Jeffrey Haessler
Fred Hutchinson Cancer Research Center, Seattle WA
Christopher R Gignoux
Stanford University, Stanford CA
Heather M Highland
University of North Carolina at Chapel Hill, Chapel Hill NC
Yesha M Patel
Keck School of Medicine, University of Southern California, Los Angeles CA
Elena P Sorokin
Stanford University, Stanford CA
Christy L Avery
University of North Carolina at Chapel Hill, Chapel Hill NC
Gillian M Belbin
Icahn School of Medicine at Mount Sinai, New York NY
Stephanie A Bien
Fred Hutchinson Cancer Research Center, Seattle WA
Iona Cheng
Cancer Prevention Institute of California, Fremont CA
Sinead Cullina
Icahn School of Medicine at Mount Sinai, New York NY
Chani J Hodonsky
University of North Carolina at Chapel Hill, Chapel Hill NC
Yao Hu
Fred Hutchinson Cancer Research Center, Seattle WA
Laura M Huckins
Icahn School of Medicine at Mount Sinai, New York NY
Janina Jeff
Icahn School of Medicine at Mount Sinai, New York NY
Anne E Justice
University of North Carolina at Chapel Hill, Chapel Hill NC
Jonathan M Kocarnik
Fred Hutchinson Cancer Research Center, Seattle WA
Unhee Lim
University of Hawaii Cancer Center, Honolulu HI
Bridget M Lin
University of North Carolina at Chapel Hill, Chapel Hill NC
Yingchang Lu
Icahn School of Medicine at Mount Sinai, New York NY
Sarah C Nelson
University of Washington, Seattle WA
Sung-Shim L Park
Keck School of Medicine, University of Southern California, Los Angeles CA
Hannah Poisner
Icahn School of Medicine at Mount Sinai, New York NY
Michael H Preuss
Icahn School of Medicine at Mount Sinai, New York NY
Melissa A Richard
Brown Foundation Institute for Molecular Medicine, The University of Texas Health Science Center, Houston TX
Claudia Schurmann
Icahn School of Medicine at Mount Sinai, New York NY
Veronica W Setiawan
Keck School of Medicine, University of Southern California, Los Angeles CA
Alexandra Sockell
Stanford University, Stanford CA
Karan Vahi
Information Sciences Institute, University of Southern California, Marina del Rey CA
Abhishek Vishnu
Icahn School of Medicine at Mount Sinai, New York NY
Marie Verbanck
Icahn School of Medicine at Mount Sinai, New York NY
Ryan Walker
Icahn School of Medicine at Mount Sinai, New York NY
Kristin L Young
University of North Carolina at Chapel Hill, Chapel Hill NC
Niha Zubair
Fred Hutchinson Cancer Research Center, Seattle WA
Victor Acuna-Alonso
Escuela Nacional de Antropologia e Historia, Mexico
Jose Luis Ambite
Information Sciences Institute, University of Southern California, Marina del Rey CA
Kathleen C Barnes
University of Colorado, Anschutz Medical Campus, Denver CO
Eric Boerwinkle
Human Genetics Center, School of Public Health, The University of Texas Health Science Center, Houston TX
Erwin Bottinger
Icahn School of Medicine at Mount Sinai, New York NY
Carlos D Bustamante
Stanford University, Stanford CA
Christian Caberto
University of Hawaii, Honolulu HI
Samuel Canizales-Quinteroes
Instituto Nacional de Medicina Genómica, Mexico
Matthew P Conomos
University of Washington, Seattle WA
Ewa Deelman
Information Sciences Institute, University of Southern California, Marina del Rey CA
Ron Do
Icahn School of Medicine at Mount Sinai, New York NY
Kimberly Doheny
Johns Hopkins University, Baltimore MD
Lindsay Fernandez-Rhodes
The Pennsylvania State University, University Park, PA
Myriam Fornage
Brown Foundation Institute for Molecular Medicine, The University of Texas Health Science Center, Houston TX
Gerardo Heiss
University of North Carolina at Chapel Hill, Chapel Hill NC
Brenna Henn
University of California, Davis CA
Lucia A Hindorff
NIH National Human Genome Research Institute, Bethesda MD
Rebecca D Jackson
Ohio State Medical Center, Columbus OH
Benyam Hailu
NIH National Institute on Minority Health and Health Disparities, Bethesda MD
Cecelia A Laurie
University of Washington, Seattle WA
Cathy C Laurie
University of Washington, Seattle WA
Yuqing Li
Cancer Prevention Institute of California, Fremont CA
Dan-Yu Lin
University of North Carolina at Chapel Hill, Chapel Hill NC
Andres Moreno-Estrada
National Laboratory of Genomics for Biodiversity (UGA-LANGEBIO), CINVESTAV-Irapuato, Mexico
Girish Nadkarni
Icahn School of Medicine at Mount Sinai, New York NY
Paul Norman
University of Colorado, Anschutz Medical Campus, Denver CO
Loreall C Pooler
Keck School of Medicine, University of Southern California, Los Angeles CA
Alexander P Reiner
University of Washington, Seattle WA
Jane Romm
Johns Hopkins University, Baltimore MD
Chiara Sabati
Stanford University, Stanford CA
Karla Sandoval
National Laboratory of Genomics for Biodiversity (UGA-LANGEBIO), CINVESTAV-Irapuato, Mexico
Xin Sheng
Keck School of Medicine, University of Southern California, Los Angeles CA
Eli A Stahl
Icahn School of Medicine at Mount Sinai, New York NY
Daniel O Stram
Keck School of Medicine, University of Southern California, Los Angeles CA
Timothy A Thornton
University of Washington, Seattle WA
Christina L Wassel
University of Vermont College of Medicine, Burlington VT
Lynne R Wilkens
University of Hawaii, Honolulu HI
Cheryl A Winkler
Frederick National Laboratory, Frederick MA
Sachi Yoneyama
University of North Carolina at Chapel Hill, Chapel Hill NC
Steven Buyske
Rutgers University, New Brunswick NJ
Chris Haiman
Keck School of Medicine, University of Southern California, Los Angeles CA
Charles Kooperberg
Fred Hutchinson Cancer Research Center, Seattle WA
Loic Le Marchand
University of Hawaii, Honolulu HI
Ruth JF Loos
Icahn School of Medicine at Mount Sinai, New York NY
Tara C Matise
Rutgers University, New Brunswick NJ
Kari E North
University of North Carolina at Chapel Hill, Chapel Hill NC
Ulrike Peters
Fred Hutchinson Cancer Research Center, Seattle WA
Eimear E Kenny
Icahn School of Medicine at Mount Sinai, New York NY
Christopher S Carlson
Fred Hutchinson Cancer Research Center, Seattle WA
Summary/Abstract
Genome-wide association studies (GWAS) have laid the foundation for investigations into the biology of complex traits, drug development, and clinical guidelines. However, the dominance of European-ancestry populations in GWAS creates a biased view of the role of human variation in disease, and hinders the equitable translation of genetic associations into clinical and public health applications. The Population Architecture using Genomics and Epidemiology (PAGE) study conducted a GWAS of 26 clinical and behavioral phenotypes in 49,839 non-European individuals. Using strategies designed for analysis of multi-ethnic and admixed populations, we confirm 574 GWAS catalog variants across these traits, and find 38 secondary signals in known loci and 27 novel loci. Our data shows strong evidence of effect-size heterogeneity across ancestries for published GWAS associations, substantial benefits for fine-mapping using diverse cohorts, and insights into clinical implications. We strongly advocate for continued, large genome-wide efforts in diverse populations to reduce health disparities.
Copyright
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
Posted October 17, 2018.
The PAGE Study: How Genetic Diversity Improves Our Understanding of the Architecture of Complex Traits
Genevieve L Wojcik, Mariaelisa Graff, Katherine K Nishimura, Ran Tao, Jeffrey Haessler, Christopher R Gignoux, Heather M Highland, Yesha M Patel, Elena P Sorokin, Christy L Avery, Gillian M Belbin, Stephanie A Bien, Iona Cheng, Sinead Cullina, Chani J Hodonsky, Yao Hu, Laura M Huckins, Janina Jeff, Anne E Justice, Jonathan M Kocarnik, Unhee Lim, Bridget M Lin, Yingchang Lu, Sarah C Nelson, Sung-Shim L Park, Hannah Poisner, Michael H Preuss, Melissa A Richard, Claudia Schurmann, Veronica W Setiawan, Alexandra Sockell, Karan Vahi, Abhishek Vishnu, Marie Verbanck, Ryan Walker, Kristin L Young, Niha Zubair, Victor Acuna-Alonso, Jose Luis Ambite, Kathleen C Barnes, Eric Boerwinkle, Erwin Bottinger, Carlos D Bustamante, Christian Caberto, Samuel Canizales-Quinteroes, Matthew P Conomos, Ewa Deelman, Ron Do, Kimberly Doheny, Lindsay Fernandez-Rhodes, Myriam Fornage, Gerardo Heiss, Brenna Henn, Lucia A Hindorff, Rebecca D Jackson, Benyam Hailu, Cecelia A Laurie, Cathy C Laurie, Yuqing Li, Dan-Yu Lin, Andres Moreno-Estrada, Girish Nadkarni, Paul Norman, Loreall C Pooler, Alexander P Reiner, Jane Romm, Chiara Sabati, Karla Sandoval, Xin Sheng, Eli A Stahl, Daniel O Stram, Timothy A Thornton, Christina L Wassel, Lynne R Wilkens, Cheryl A Winkler, Sachi Yoneyama, Steven Buyske, Chris Haiman, Charles Kooperberg, Loic Le Marchand, Ruth JF Loos, Tara C Matise, Kari E North, Ulrike Peters, Eimear E Kenny, Christopher S Carlson
bioRxiv 188094; doi: https://doi.org/10.1101/188094
The PAGE Study: How Genetic Diversity Improves Our Understanding of the Architecture of Complex Traits
Genevieve L Wojcik, Mariaelisa Graff, Katherine K Nishimura, Ran Tao, Jeffrey Haessler, Christopher R Gignoux, Heather M Highland, Yesha M Patel, Elena P Sorokin, Christy L Avery, Gillian M Belbin, Stephanie A Bien, Iona Cheng, Sinead Cullina, Chani J Hodonsky, Yao Hu, Laura M Huckins, Janina Jeff, Anne E Justice, Jonathan M Kocarnik, Unhee Lim, Bridget M Lin, Yingchang Lu, Sarah C Nelson, Sung-Shim L Park, Hannah Poisner, Michael H Preuss, Melissa A Richard, Claudia Schurmann, Veronica W Setiawan, Alexandra Sockell, Karan Vahi, Abhishek Vishnu, Marie Verbanck, Ryan Walker, Kristin L Young, Niha Zubair, Victor Acuna-Alonso, Jose Luis Ambite, Kathleen C Barnes, Eric Boerwinkle, Erwin Bottinger, Carlos D Bustamante, Christian Caberto, Samuel Canizales-Quinteroes, Matthew P Conomos, Ewa Deelman, Ron Do, Kimberly Doheny, Lindsay Fernandez-Rhodes, Myriam Fornage, Gerardo Heiss, Brenna Henn, Lucia A Hindorff, Rebecca D Jackson, Benyam Hailu, Cecelia A Laurie, Cathy C Laurie, Yuqing Li, Dan-Yu Lin, Andres Moreno-Estrada, Girish Nadkarni, Paul Norman, Loreall C Pooler, Alexander P Reiner, Jane Romm, Chiara Sabati, Karla Sandoval, Xin Sheng, Eli A Stahl, Daniel O Stram, Timothy A Thornton, Christina L Wassel, Lynne R Wilkens, Cheryl A Winkler, Sachi Yoneyama, Steven Buyske, Chris Haiman, Charles Kooperberg, Loic Le Marchand, Ruth JF Loos, Tara C Matise, Kari E North, Ulrike Peters, Eimear E Kenny, Christopher S Carlson
bioRxiv 188094; doi: https://doi.org/10.1101/188094
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