Abstract

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.

Date

September 15, 2017

Authors

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, Chani J Hodonsky, 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, Michael H Preuss, Melissa A Richard, Claudia Schurmann, Veronica W Setiawan, Karan Vahi, Abhishek Vishnu, Marie Verbanck, Ryan Walker, Kristin L Young, Niha Zubair, Jose Luis Ambite, Eric Boerwinkle, Erwin Bottinger, Carlos D Bustamante, Christian Caberto, Matthew P Conomos, Ewa Deelman, Ron Do, Kimberly Doheny, Lindsay Fernandez-Rhodes, Myriam Fornage, Gerardo Heiss, Lucia A Hindorff, Rebecca D Jackson, Regina James, Cecelia A Laurie, Cathy C Laurie, Yuqing Li, Dan-Yu Lin, Girish Nadkarni, Loreall C Pooler, Alexander P Reiner, Jane Romm, Chiara Sabati, Xin Sheng, Eli A Stahl, Daniel O Stram, Timothy A Thornton, Christina L Wassel, Lynne R Wilkens, 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

Journal

BioRxiv

Pages

188094

Publisher

Cold Spring Harbor Laboratory