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

Research output: Contribution to journalJournal articleResearchpeer-review

  • Ming-Huei Chen
  • Laura M. Raffield
  • Abdou Mousas
  • Saori Sakaue
  • Jennifer E. Huffman
  • Arden Moscati
  • Bhavi Trivedi
  • Tao Jiang
  • Parsa Akbari
  • Dragana Vuckovic
  • Erik L. Bao
  • Xue Zhong
  • Regina Manansala
  • Veronique Laplante
  • Minhui Chen
  • Ken Sin Lo
  • Huijun Qian
  • Caleb A. Lareau
  • Melissa Beaudoin
  • Karen A. Hunt
  • Masato Akiyama
  • Traci M. Bartz
  • Yoav Ben-Shlomo
  • Andrew Beswick
  • Jette Bork-Jensen
  • Erwin P. Bottinger
  • Jennifer A. Brody
  • Frank J. A. van Rooij
  • Kumaraswamynaidu Chitrala
  • Kelly Cho
  • Helene Choquet
  • Adolfo Correa
  • John Danesh
  • Emanuele Di Angelantonio
  • Niki Dimou
  • Jingzhong Ding
  • Paul Elliott
  • Tonu Esko
  • Michele K. Evans
  • James S. Floyd
  • Linda Broer
  • Grarup, Niels
  • Michael H. Guo
  • Andreas Greinacher
  • Jeff Haessler
  • Hansen, Torben
  • Joanna M. M. Howson
  • Linneberg, Allan René
  • Pedersen, Oluf Borbye
  • Ruth J. F. Loos
  • VA Million Veteran Program

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 <5310(-9), including 71 novel associations not found in EUR populations. We also identified 28 additional novel variants in ancestry-specific, non-EURmeta-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
JournalCell
Volume182
Issue number5
Pages (from-to)1198-+
Number of pages30
ISSN0092-8674
DOIs
Publication statusPublished - 2020

    Research areas

  • GENOME-WIDE ASSOCIATION, FREQUENCY CODING VARIANTS, POLYGENIC RISK SCORES, HUMAN HEMATOPOIESIS, AFRICAN-AMERICANS, SINGLE-CELL, BIOBANK, LOCI, DISEASE, TRAIT

ID: 250075688