Multi-Ethnic Genome-Wide Association Analyses of White Blood Cell and Platelet Traits in the Population Architecture Using Genomics and Epidemiology (PAGE) Study

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Citation

Hu, Yao; Bien, Stephanie A.; Nishimura, Katherine K.; Haessler, Jeffrey; Hodonsky, Chani J.; Baldassari, Antoine R.; Highland, Heather M.; Wang, Zhe; Preuss, Michael H.; & Sitlani, Colleen M., et al. (2021). Multi-Ethnic Genome-Wide Association Analyses of White Blood Cell and Platelet Traits in the Population Architecture Using Genomics and Epidemiology (PAGE) Study. BMC Genomics, 22(1), 432. PMCID: PMC8191001

Abstract

BACKGROUND: Circulating white blood cell and platelet traits are clinically linked to various disease outcomes and differ across individuals and ancestry groups. Genetic factors play an important role in determining these traits and many loci have been identified. However, most of these findings were identified in populations of European ancestry (EA), with African Americans (AA), Hispanics/Latinos (HL), and other races/ethnicities being severely underrepresented.
RESULTS: We performed ancestry-combined and ancestry-specific genome-wide association studies (GWAS) for white blood cell and platelet traits in the ancestrally diverse Population Architecture using Genomics and Epidemiology (PAGE) Study, including 16,201 AA, 21,347 HL, and 27,236 EA participants. We identified six novel findings at suggestive significance (P < 5E-8), which need confirmation, and independent signals at six previously established regions at genome-wide significance (P < 2E-9). We confirmed multiple previously reported genome-wide significant variants in the single variant association analysis and multiple genes using PrediXcan. Evaluation of loci reported from a Euro-centric GWAS indicated attenuation of effect estimates in AA and HL compared to EA populations.
CONCLUSIONS: Our results highlighted the potential to identify ancestry-specific and ancestry-agnostic variants in participants with diverse backgrounds and advocate for continued efforts in improving inclusion of racially/ethnically diverse populations in genetic association studies for complex traits.

URL

http://dx.doi.org/10.1186/s12864-021-07745-5

Reference Type

Journal Article

Year Published

2021

Journal Title

BMC Genomics

Author(s)

Hu, Yao
Bien, Stephanie A.
Nishimura, Katherine K.
Haessler, Jeffrey
Hodonsky, Chani J.
Baldassari, Antoine R.
Highland, Heather M.
Wang, Zhe
Preuss, Michael H.
Sitlani, Colleen M.
Wojcik, Genevieve L.
Tao, Ran
Graff, Mariaelisa
Huckins, Laura M.
Sun, Quan
Chen, Ming-Huei
Mousas, Abdou
Auer, Paul L.
Lettre, Guillaume
Blood Cell Consortium,
Tang, Weihong
Qi, Lihong
Thyagarajan, Bharat
Buyske, Steven G.
Fornage, Myriam
Hindorff, Lucia A.
Li, Yun
Lin, Danyu
Reiner, Alexander P.
North, Kari E.
Loos, Ruth J. F.
Raffield, Laura M.
Peters, Ulrike
Avery, Christy L.
Kooperberg, Charles

Article Type

Regular

PMCID

PMC8191001

Data Set/Study

Population Architecture using Genomics and Epidemiology (PAGE) Study

Race/Ethnicity

European Ancestry
African Ancestry
Hispanic Ancestry

ORCiD

Avery - 0000-0002-1044-8162