Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations

VA Million Veteran Program, Guillaume Lettre*, Paul L. Auer*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

Abstract

Most loci identified by GWASs have been found in populations of European ancestry (EUR). In trans-ethnic meta-analyses for 15 hematological traits in 746,667 participants, including 184,535 non-EUR individuals, we identified 5,552 trait-variant associations at p < 5 × 10-9, including 71 novel associations not found in EUR populations. We also identified 28 additional novel variants in ancestry-specific, non-EUR meta-analyses, including an IL7 missense variant in South Asians associated with lymphocyte count in vivo and IL-7 secretion levels in vitro. Fine-mapping prioritized variants annotated as functional and generated 95% credible sets that were 30% smaller when using the trans-ethnic as opposed to the EUR-only results. We explored the clinical significance and predictive value of trans-ethnic variants in multiple populations and compared genetic architecture and the effect of natural selection on these blood phenotypes between populations. Altogether, our results for hematological traits highlight the value of a more global representation of populations in genetic studies.

Original languageEnglish
Pages (from-to)1198-1213.e14
JournalCell
Volume182
Issue number5
DOIs
Publication statusPublished - 3 Sep 2020

Bibliographical note

Copyright © 2020 Elsevier Inc. All rights reserved.

Keywords

  • interleukin-7
  • genetic architecture
  • fine-mapping
  • selective sweeps
  • polygenic trait score
  • phenome-wide association study

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