Genetic analyses of diverse populations improves discovery for 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, Marie Verbanck, Abhishek Vishnu, Ryan W. Walker, Kristin L. Young, Niha Zubair, Victor Acuña-Alonso, Jose Luis Ambite, Kathleen C. Barnes, Eric Boerwinkle, Erwin P. Bottinger, Carlos D. Bustamante, Christian Caberto, Samuel Canizales-Quinteros, Matthew P. Conomos, Ewa Deelman, Ron Do, Kimberly Doheny, Lindsay Fernández-Rhodes, Myriam Fornage, Benyam Hailu, Gerardo Heiss, Brenna M. Henn, Lucia A. Hindorff, Rebecca D. Jackson, Cecelia A. Laurie, Cathy C. Laurie, Yuqing Li, Dan Yu Lin, Andres Moreno-Estrada, Girish Nadkarni, Paul J. Norman, Loreall C. Pooler, Alexander P. Reiner, Jane Romm, Chiara Sabatti, 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, Christopher A. Haiman, Charles Kooperberg, Loic Le Marchand, Ruth J.F. Loos, Tara C. Matise, Kari E. North, Ulrike Peters, Eimear E. Kenny, Christopher S. Carlson

Research output: Contribution to journalArticlepeer-review

527 Scopus citations


Genome-wide association studies (GWAS) have laid the foundation for investigations into the biology of complex traits, drug development and clinical guidelines. However, the majority of discovery efforts are based on data from populations of European ancestry1–3. In light of the differential genetic architecture that is known to exist between populations, bias in representation can exacerbate existing disease and healthcare disparities. Critical variants may be missed if they have a low frequency or are completely absent in European populations, especially as the field shifts its attention towards rare variants, which are more likely to be population-specific4–10. Additionally, effect sizes and their derived risk prediction scores derived in one population may not accurately extrapolate to other populations11,12. Here we demonstrate the value of diverse, multi-ethnic participants in large-scale genomic studies. The Population Architecture using Genomics and Epidemiology (PAGE) study conducted a GWAS of 26 clinical and behavioural phenotypes in 49,839 non-European individuals. Using strategies tailored for analysis of multi-ethnic and admixed populations, we describe a framework for analysing diverse populations, identify 27 novel loci and 38 secondary signals at known loci, as well as replicate 1,444 GWAS catalogue associations across these traits. Our data show evidence of effect-size heterogeneity across ancestries for published GWAS associations, substantial benefits for fine-mapping using diverse cohorts and insights into clinical implications. In the United States—where minority populations have a disproportionately higher burden of chronic conditions13—the lack of representation of diverse populations in genetic research will result in inequitable access to precision medicine for those with the highest burden of disease. We strongly advocate for continued, large genome-wide efforts in diverse populations to maximize genetic discovery and reduce health disparities.

Original languageEnglish
Pages (from-to)514-518
Number of pages5
Issue number7762
StatePublished - 27 Jun 2019


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