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The PAGE Study: How Genetic Diversity Improves Our Understanding of the Architecture of Complex Traits

By 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

Posted 15 Sep 2017
bioRxiv DOI: 10.1101/188094

Genome-wide association studies (GWAS) have laid the foundation for many downstream investigations, including the biology of complex traits, drug development, and clinical guidelines. However, the dominance of European-ancestry populations in GWAS creates a biased view of human variation and hinders the translation of genetic associations into clinical and public health applications. To demonstrate the benefit of studying underrepresented populations, 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 novel strategies for multi-ethnic analysis of admixed populations, we confirm 574 GWAS catalog variants across these traits, and find 28 novel loci and 42 residual signals in known loci. Our data show strong evidence of effect-size heterogeneity across ancestries for published GWAS associations, which substantially restricts genetically-guided precision medicine. We advocate for new, large genome-wide efforts in diverse populations to reduce health disparities.

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