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 J.F. Loos; Tara C. Matise; Kari E. North; Ulrike Peters; Eimear E. Kenny; Christopher S. Carlson

doi: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. KocarnikUnhee 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 J.F. Loos, Tara C. Matise, Kari E. North, Ulrike Peters, Eimear E. Kenny, Christopher S. Carlson

School of Medicine

Research output: Contribution to journal › Article › peer-review

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 multiethnic 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.

Original language	English (US)
Journal	Unknown Journal
DOIs	https://doi.org/10.1101/188094
State	Published - Sep 15 2017

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
Immunology and Microbiology(all)
Neuroscience(all)
Pharmacology, Toxicology and Pharmaceutics(all)

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Wojcik, G. L., Graff, M., Nishimura, K. K., Tao, R., Haessler, J., Gignoux, C. R., Highland, H. M., Patel, Y. M., Sorokin, E. P., Avery, C. L., Belbin, G. M., Bien, S. A., Cheng, I., Cullina, S., Hodonsky, C. J., Hu, Y., Huckins, L. M., Jeff, J., Justice, A. E., ... Carlson, C. S. (2017). The PAGE Study: How genetic diversity improves our understanding of the architecture of complex traits. Unknown Journal. https://doi.org/10.1101/188094

The PAGE Study : How genetic diversity improves our understanding of the architecture of complex traits. / Wojcik, Genevieve L.; Graff, Mariaelisa; Nishimura, Katherine K.; Tao, Ran; Haessler, Jeffrey; Gignoux, Christopher R.; Highland, Heather M.; Patel, Yesha M.; Sorokin, Elena P.; Avery, Christy L.; Belbin, Gillian M.; Bien, Stephanie A.; Cheng, Iona; Cullina, Sinead; Hodonsky, Chani J.; Hu, Yao; Huckins, Laura M.; Jeff, Janina; Justice, Anne E.; Kocarnik, Jonathan M.; Lim, Unhee; Lin, Bridget M.; Lu, Yingchang; Nelson, Sarah C.; Park, Sung Shim L.; Poisner, Hannah; Preuss, Michael H.; Richard, Melissa A.; Schurmann, Claudia; Setiawan, Veronica W.; Sockell, Alexandra; Vahi, Karan; Vishnu, Abhishek; Verbanck, Marie; Walker, Ryan; Young, Kristin L.; Zubair, Niha; Acuna-Alonso, Victor; Ambite, Jose Luis; Barnes, Kathleen C.; Boerwinkle, Eric; Bottinger, Erwin; Bustamante, Carlos D.; Caberto, Christian; Canizales-Quinteroes, Samuel; Conomos, Matthew P.; Deelman, Ewa; Do, Ron; Doheny, Kimberly; Fernandez -Rhodes, Lindsay; Fornage, Myriam; Heiss, Gerardo; Henn, Brenna; Hindorff, Lucia A.; Jackson, Rebecca D.; Hailu, Benyam; Laurie, Cecelia A.; Laurie, Cathy C.; Li, Yuqing; Lin, Dan Yu; Moreno-Estrada, Andres; Nadkarni, Girish; Norman, Paul; Pooler, Loreall C.; Reiner, Alexander P.; Romm, Jane; Sabati, Chiara; Sandoval, Karla; Sheng, Xin; Stahl, Eli A.; Stram, Daniel O.; Thornton, Timothy A.; Wassel, Christina L.; Wilkens, Lynne R.; Winkler, Cheryl A.; Yoneyama, Sachi; Buyske, Steven; Haiman, Chris; Kooperberg, Charles; Le Marchand, Loic; Loos, Ruth J.F.; Matise, Tara C.; North, Kari E.; Peters, Ulrike; Kenny, Eimear E.; Carlson, Christopher S.

In: Unknown Journal, 15.09.2017.

Research output: Contribution to journal › Article › peer-review

Wojcik, GL, Graff, M, Nishimura, KK, Tao, R, Haessler, J, Gignoux, CR, Highland, HM, Patel, YM, Sorokin, EP, Avery, CL, Belbin, GM, Bien, SA, Cheng, I, Cullina, S, Hodonsky, CJ, Hu, Y, Huckins, LM, Jeff, J, Justice, AE, Kocarnik, JM, Lim, U, Lin, BM, Lu, Y, Nelson, SC, Park, SSL, Poisner, H, Preuss, MH, Richard, MA, Schurmann, C, Setiawan, VW, Sockell, A, Vahi, K, Vishnu, A, Verbanck, M, Walker, R, Young, KL, Zubair, N, Acuna-Alonso, V, Ambite, JL, Barnes, KC, Boerwinkle, E, Bottinger, E, Bustamante, CD, Caberto, C, Canizales-Quinteroes, S, Conomos, MP, Deelman, E, Do, R, Doheny, K, Fernandez -Rhodes, L, Fornage, M, Heiss, G, Henn, B, Hindorff, LA, Jackson, RD, Hailu, B, Laurie, CA, Laurie, CC, Li, Y, Lin, DY, Moreno-Estrada, A, Nadkarni, G, Norman, P, Pooler, LC, Reiner, AP, Romm, J, Sabati, C, Sandoval, K, Sheng, X, Stahl, EA, Stram, DO, Thornton, TA, Wassel, CL, Wilkens, LR, Winkler, CA, Yoneyama, S, Buyske, S, Haiman, C, Kooperberg, C, Le Marchand, L, Loos, RJF, Matise, TC, North, KE, Peters, U, Kenny, EE & Carlson, CS 2017, 'The PAGE Study: How genetic diversity improves our understanding of the architecture of complex traits', Unknown Journal. https://doi.org/10.1101/188094

Wojcik, Genevieve L. ; Graff, Mariaelisa ; Nishimura, Katherine K. ; Tao, Ran ; Haessler, Jeffrey ; Gignoux, Christopher R. ; Highland, Heather M. ; Patel, Yesha M. ; Sorokin, Elena P. ; Avery, Christy L. ; Belbin, Gillian M. ; Bien, Stephanie A. ; Cheng, Iona ; Cullina, Sinead ; Hodonsky, Chani J. ; Hu, Yao ; Huckins, Laura M. ; Jeff, Janina ; Justice, Anne E. ; Kocarnik, Jonathan M. ; Lim, Unhee ; Lin, Bridget M. ; Lu, Yingchang ; Nelson, Sarah C. ; Park, Sung Shim L. ; Poisner, Hannah ; Preuss, Michael H. ; Richard, Melissa A. ; Schurmann, Claudia ; Setiawan, Veronica W. ; Sockell, Alexandra ; Vahi, Karan ; Vishnu, Abhishek ; Verbanck, Marie ; Walker, Ryan ; Young, Kristin L. ; Zubair, Niha ; Acuna-Alonso, Victor ; Ambite, Jose Luis ; Barnes, Kathleen C. ; Boerwinkle, Eric ; Bottinger, Erwin ; Bustamante, Carlos D. ; Caberto, Christian ; Canizales-Quinteroes, Samuel ; Conomos, Matthew P. ; Deelman, Ewa ; Do, Ron ; Doheny, Kimberly ; Fernandez -Rhodes, Lindsay ; Fornage, Myriam ; Heiss, Gerardo ; Henn, Brenna ; Hindorff, Lucia A. ; Jackson, Rebecca D. ; Hailu, Benyam ; Laurie, Cecelia A. ; Laurie, Cathy C. ; Li, Yuqing ; Lin, Dan Yu ; Moreno-Estrada, Andres ; Nadkarni, Girish ; Norman, Paul ; Pooler, Loreall C. ; Reiner, Alexander P. ; Romm, Jane ; Sabati, Chiara ; Sandoval, Karla ; Sheng, Xin ; Stahl, Eli A. ; Stram, Daniel O. ; Thornton, Timothy A. ; Wassel, Christina L. ; Wilkens, Lynne R. ; Winkler, Cheryl A. ; Yoneyama, Sachi ; Buyske, Steven ; Haiman, Chris ; Kooperberg, Charles ; Le Marchand, Loic ; Loos, Ruth J.F. ; Matise, Tara C. ; North, Kari E. ; Peters, Ulrike ; Kenny, Eimear E. ; Carlson, Christopher S. / The PAGE Study : How genetic diversity improves our understanding of the architecture of complex traits. In: Unknown Journal. 2017.

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title = "The PAGE Study: How genetic diversity improves our understanding of the architecture of complex traits",

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 multiethnic 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.",

author = "Wojcik, {Genevieve L.} and Mariaelisa Graff and Nishimura, {Katherine K.} and Ran Tao and Jeffrey Haessler and Gignoux, {Christopher R.} and Highland, {Heather M.} and Patel, {Yesha M.} and Sorokin, {Elena P.} and Avery, {Christy L.} and Belbin, {Gillian M.} and Bien, {Stephanie A.} and Iona Cheng and Sinead Cullina and Hodonsky, {Chani J.} and Yao Hu and Huckins, {Laura M.} and Janina Jeff and Justice, {Anne E.} and Kocarnik, {Jonathan M.} and Unhee Lim and Lin, {Bridget M.} and Yingchang Lu and Nelson, {Sarah C.} and Park, {Sung Shim L.} and Hannah Poisner and Preuss, {Michael H.} and Richard, {Melissa A.} and Claudia Schurmann and Setiawan, {Veronica W.} and Alexandra Sockell and Karan Vahi and Abhishek Vishnu and Marie Verbanck and Ryan Walker and Young, {Kristin L.} and Niha Zubair and Victor Acuna-Alonso and Ambite, {Jose Luis} and Barnes, {Kathleen C.} and Eric Boerwinkle and Erwin Bottinger and Bustamante, {Carlos D.} and Christian Caberto and Samuel Canizales-Quinteroes and Conomos, {Matthew P.} and Ewa Deelman and Ron Do and Kimberly Doheny and {Fernandez -Rhodes}, Lindsay and Myriam Fornage and Gerardo Heiss and Brenna Henn and Hindorff, {Lucia A.} and Jackson, {Rebecca D.} and Benyam Hailu and Laurie, {Cecelia A.} and Laurie, {Cathy C.} and Yuqing Li and Lin, {Dan Yu} and Andres Moreno-Estrada and Girish Nadkarni and Paul Norman and Pooler, {Loreall C.} and Reiner, {Alexander P.} and Jane Romm and Chiara Sabati and Karla Sandoval and Xin Sheng and Stahl, {Eli A.} and Stram, {Daniel O.} and Thornton, {Timothy A.} and Wassel, {Christina L.} and Wilkens, {Lynne R.} and Winkler, {Cheryl A.} and Sachi Yoneyama and Steven Buyske and Chris Haiman and Charles Kooperberg and {Le Marchand}, Loic and Loos, {Ruth J.F.} and Matise, {Tara C.} and North, {Kari E.} and Ulrike Peters and Kenny, {Eimear E.} and Carlson, {Christopher S.}",

note = "Publisher 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. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

year = "2017",

month = sep,

day = "15",

doi = "10.1101/188094",

language = "English (US)",

journal = "Advances in Water Resources",

issn = "0309-1708",

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TY - JOUR

T1 - The PAGE Study

T2 - How genetic diversity improves our understanding of the architecture of complex traits

AU - Wojcik, Genevieve L.

AU - Graff, Mariaelisa

AU - Nishimura, Katherine K.

AU - Tao, Ran

AU - Haessler, Jeffrey

AU - Gignoux, Christopher R.

AU - Highland, Heather M.

AU - Patel, Yesha M.

AU - Sorokin, Elena P.

AU - Avery, Christy L.

AU - Belbin, Gillian M.

AU - Bien, Stephanie A.

AU - Cheng, Iona

AU - Cullina, Sinead

AU - Hodonsky, Chani J.

AU - Hu, Yao

AU - Huckins, Laura M.

AU - Jeff, Janina

AU - Justice, Anne E.

AU - Kocarnik, Jonathan M.

AU - Lim, Unhee

AU - Lin, Bridget M.

AU - Lu, Yingchang

AU - Nelson, Sarah C.

AU - Park, Sung Shim L.

AU - Poisner, Hannah

AU - Preuss, Michael H.

AU - Richard, Melissa A.

AU - Schurmann, Claudia

AU - Setiawan, Veronica W.

AU - Sockell, Alexandra

AU - Vahi, Karan

AU - Vishnu, Abhishek

AU - Verbanck, Marie

AU - Walker, Ryan

AU - Young, Kristin L.

AU - Zubair, Niha

AU - Acuna-Alonso, Victor

AU - Ambite, Jose Luis

AU - Barnes, Kathleen C.

AU - Boerwinkle, Eric

AU - Bottinger, Erwin

AU - Bustamante, Carlos D.

AU - Caberto, Christian

AU - Canizales-Quinteroes, Samuel

AU - Conomos, Matthew P.

AU - Deelman, Ewa

AU - Do, Ron

AU - Doheny, Kimberly

AU - Fernandez -Rhodes, Lindsay

AU - Fornage, Myriam

AU - Heiss, Gerardo

AU - Henn, Brenna

AU - Hindorff, Lucia A.

AU - Jackson, Rebecca D.

AU - Hailu, Benyam

AU - Laurie, Cecelia A.

AU - Laurie, Cathy C.

AU - Li, Yuqing

AU - Lin, Dan Yu

AU - Moreno-Estrada, Andres

AU - Nadkarni, Girish

AU - Norman, Paul

AU - Pooler, Loreall C.

AU - Reiner, Alexander P.

AU - Romm, Jane

AU - Sabati, Chiara

AU - Sandoval, Karla

AU - Sheng, Xin

AU - Stahl, Eli A.

AU - Stram, Daniel O.

AU - Thornton, Timothy A.

AU - Wassel, Christina L.

AU - Wilkens, Lynne R.

AU - Winkler, Cheryl A.

AU - Yoneyama, Sachi

AU - Buyske, Steven

AU - Haiman, Chris

AU - Kooperberg, Charles

AU - Le Marchand, Loic

AU - Loos, Ruth J.F.

AU - Matise, Tara C.

AU - North, Kari E.

AU - Peters, Ulrike

AU - Kenny, Eimear E.

AU - Carlson, Christopher S.

N1 - Publisher 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. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2017/9/15

Y1 - 2017/9/15

N2 - 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 multiethnic 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.

AB - 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 multiethnic 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.

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