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

Accepted version
Peer-reviewed

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Type

Article

Change log

Authors

Chen, Ming-Huei 
Raffield, Laura M 
Mousas, Abdou 
Sakaue, Saori 
Huffman, Jennifer E 

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.

Description

Keywords

interleukin-7, genetic architecture, fine-mapping, selective sweeps, polygenic trait score, phenome-wide association study, Asian People, Genetics, Genome-Wide Association Study, HEK293 Cells, Humans, Interleukin-7, Mutation, Missense, Phenotype, Polymorphism, Single Nucleotide, White People

Journal Title

Cell

Conference Name

Journal ISSN

0092-8674
1097-4172

Volume Title

182

Publisher

Elsevier BV