Multi-ethnic genome-wide association analyses of white blood cell and platelet traits in the Population Architecture using Genomics and Epidemiology (PAGE) study

the Blood Cell Consortium

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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.

Original languageEnglish (US)
Article number432
JournalBMC Genomics
Volume22
Issue number1
DOIs
StatePublished - Dec 2021

Bibliographical note

Funding Information:
BioMe: Data of BioMe Biobank used in this study was provided by the Charles Bronfman Institute for Personalized Medicine at the Icahn School of Medicine at Mount Sinai. Phenotype data collection was supported by the Andrea and Charles Bronfman Philanthropies.

Funding Information:
The PAGE Study is funded by the National Human Genome Research Institute (NHGRI) with co-funding from the National Institute on Minority Health and Health Disparities (NIMHD). The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University. Genotype data quality control and quality assurance services were provided by the Genetic Analysis Center in the Biostatistics Department of the University of Washington, through support provided by the CIDR contract.

Funding Information:
ARIC: The Atherosclerosis Risk in Communities study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services (contract numbers HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700004I and HHSN268201700005I), R01HL087641, R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. The authors thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research.

Publisher Copyright:
© 2021, The Author(s).

Keywords

  • GWAS
  • Multi-ethnic
  • Platelets
  • White blood cells
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Phenotype
  • Genomics
  • Humans
  • Polymorphism, Single Nucleotide
  • Leukocytes

PubMed: MeSH publication types

  • Journal Article

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