Trans-ethnic meta-analysis of white blood cell phenotypes

CHARGE Hematology, COGENT, BioBank Japan Project (RIKEN) Working Groups

研究成果: Article

18 引用 (Scopus)

抄録

White blood cell (WBC) count is a common clinical measure used as a predictor of certain aspects of human health, including immunity and infection status. WBC count is also a complex trait that varies among individuals and ancestry groups. Differences in linkage disequilibrium structure and heterogeneity in allelic effects are expected to play a role in the associations observed between populations. Prior genome-wide association study (GWAS) meta-analyses have identified genomic loci associated with WBC and its subtypes, but much of the heritability of these phenotypes remains unexplained. Using GWAS summary statistics for over 50 000 individuals from three diverse populations (Japanese, African-American and European ancestry), a Bayesian model methodology was employed to account for heterogeneity between ancestry groups. This approach was used to perform a trans-ethnic meta-analysis of total WBC, neutrophil and monocyte counts. Ten previously known associations were replicated and six new loci were identified, including several regions harboring genes related to inflammation and immune cell function. Ninety-five percent credible interval regions were calculated to narrow the association signals and fine-map the putatively causal variants within loci. Finally, a conditional analysis was performed on the most significant SNPs identified by the trans-ethnic meta-analysis (MA), and nine secondary signals within loci previously associated with WBC or its subtypes were identified. This work illustrates the potential of trans-ethnic analysis and ascribes a critical role to multi-ethnic cohorts and consortia in exploring complex phenotypes with respect to variants that lie outside the European-biased GWAS pool.

元の言語English
ページ(範囲)6944-6960
ページ数17
ジャーナルHuman molecular genetics
23
発行部数25
DOI
出版物ステータスPublished - 20-12-2014

Fingerprint

Genome-Wide Association Study
Meta-Analysis
Leukocytes
Phenotype
Leukocyte Count
Linkage Disequilibrium
African Americans
Population
Single Nucleotide Polymorphism
Monocytes
Immunity
Neutrophils
Inflammation
Health
Infection
Genes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

これを引用

CHARGE Hematology, COGENT, & BioBank Japan Project (RIKEN) Working Groups (2014). Trans-ethnic meta-analysis of white blood cell phenotypes. Human molecular genetics, 23(25), 6944-6960. https://doi.org/10.1093/hmg/ddu401
CHARGE Hematology ; COGENT ; BioBank Japan Project (RIKEN) Working Groups. / Trans-ethnic meta-analysis of white blood cell phenotypes. :: Human molecular genetics. 2014 ; 巻 23, 番号 25. pp. 6944-6960.
@article{db8cc7f9ff46400fae84d8f71fe05159,
title = "Trans-ethnic meta-analysis of white blood cell phenotypes",
abstract = "White blood cell (WBC) count is a common clinical measure used as a predictor of certain aspects of human health, including immunity and infection status. WBC count is also a complex trait that varies among individuals and ancestry groups. Differences in linkage disequilibrium structure and heterogeneity in allelic effects are expected to play a role in the associations observed between populations. Prior genome-wide association study (GWAS) meta-analyses have identified genomic loci associated with WBC and its subtypes, but much of the heritability of these phenotypes remains unexplained. Using GWAS summary statistics for over 50 000 individuals from three diverse populations (Japanese, African-American and European ancestry), a Bayesian model methodology was employed to account for heterogeneity between ancestry groups. This approach was used to perform a trans-ethnic meta-analysis of total WBC, neutrophil and monocyte counts. Ten previously known associations were replicated and six new loci were identified, including several regions harboring genes related to inflammation and immune cell function. Ninety-five percent credible interval regions were calculated to narrow the association signals and fine-map the putatively causal variants within loci. Finally, a conditional analysis was performed on the most significant SNPs identified by the trans-ethnic meta-analysis (MA), and nine secondary signals within loci previously associated with WBC or its subtypes were identified. This work illustrates the potential of trans-ethnic analysis and ascribes a critical role to multi-ethnic cohorts and consortia in exploring complex phenotypes with respect to variants that lie outside the European-biased GWAS pool.",
author = "{CHARGE Hematology} and COGENT and {BioBank Japan Project (RIKEN) Working Groups} and Keller, {Margaux F.} and Reiner, {Alexander P.} and Yukinori Okada and {van Rooij}, {Frank J.A.} and Johnson, {Andrew D.} and Chen, {Ming Huei} and Smith, {Albert V.} and Morris, {Andrew P.} and Toshiko Tanaka and Luigi Ferrucci and Zonderman, {Alan B.} and Guillaume Lettre and Tamara Harris and Melissa Garcia and Stefania Bandinelli and Rehan Qayyum and Yanek, {Lisa R.} and Becker, {Diane M.} and Becker, {Lewis C.} and Charles Kooperberg and Brendan Keating and Jared Reis and Hua Tang and Eric Boerwinkle and Yoichiro Kamatani and Koichi Matsuda and Naoyuki Kamatani and Yusuke Nakamura and Michiaki Kubo and Simin Liu and Abbas Dehghan and Felix, {Janine F.} and Albert Hofman and Uitterlinden, {Andr{\'e} G.} and {van Duijn}, {Cornelia M.} and Franco, {Oscar H.} and Longo, {Dan L.} and Singleton, {Andrew B.} and Psaty, {Bruce M.} and Evans, {Michelle K.} and Cupples, {L. Adrienne} and Rotter, {Jerome I.} and O'Donnell, {Christopher J.} and Michiaki Kubo and Wilson, {James G.} and Ganesh, {Santhi K.} and Nalls, {Mike A.}",
year = "2014",
month = "12",
day = "20",
doi = "10.1093/hmg/ddu401",
language = "English",
volume = "23",
pages = "6944--6960",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "25",

}

CHARGE Hematology, COGENT & BioBank Japan Project (RIKEN) Working Groups 2014, 'Trans-ethnic meta-analysis of white blood cell phenotypes', Human molecular genetics, 巻. 23, 番号 25, pp. 6944-6960. https://doi.org/10.1093/hmg/ddu401

Trans-ethnic meta-analysis of white blood cell phenotypes. / CHARGE Hematology; COGENT; BioBank Japan Project (RIKEN) Working Groups.

:: Human molecular genetics, 巻 23, 番号 25, 20.12.2014, p. 6944-6960.

研究成果: Article

TY - JOUR

T1 - Trans-ethnic meta-analysis of white blood cell phenotypes

AU - CHARGE Hematology

AU - COGENT

AU - BioBank Japan Project (RIKEN) Working Groups

AU - Keller, Margaux F.

AU - Reiner, Alexander P.

AU - Okada, Yukinori

AU - van Rooij, Frank J.A.

AU - Johnson, Andrew D.

AU - Chen, Ming Huei

AU - Smith, Albert V.

AU - Morris, Andrew P.

AU - Tanaka, Toshiko

AU - Ferrucci, Luigi

AU - Zonderman, Alan B.

AU - Lettre, Guillaume

AU - Harris, Tamara

AU - Garcia, Melissa

AU - Bandinelli, Stefania

AU - Qayyum, Rehan

AU - Yanek, Lisa R.

AU - Becker, Diane M.

AU - Becker, Lewis C.

AU - Kooperberg, Charles

AU - Keating, Brendan

AU - Reis, Jared

AU - Tang, Hua

AU - Boerwinkle, Eric

AU - Kamatani, Yoichiro

AU - Matsuda, Koichi

AU - Kamatani, Naoyuki

AU - Nakamura, Yusuke

AU - Kubo, Michiaki

AU - Liu, Simin

AU - Dehghan, Abbas

AU - Felix, Janine F.

AU - Hofman, Albert

AU - Uitterlinden, André G.

AU - van Duijn, Cornelia M.

AU - Franco, Oscar H.

AU - Longo, Dan L.

AU - Singleton, Andrew B.

AU - Psaty, Bruce M.

AU - Evans, Michelle K.

AU - Cupples, L. Adrienne

AU - Rotter, Jerome I.

AU - O'Donnell, Christopher J.

AU - Kubo, Michiaki

AU - Wilson, James G.

AU - Ganesh, Santhi K.

AU - Nalls, Mike A.

PY - 2014/12/20

Y1 - 2014/12/20

N2 - White blood cell (WBC) count is a common clinical measure used as a predictor of certain aspects of human health, including immunity and infection status. WBC count is also a complex trait that varies among individuals and ancestry groups. Differences in linkage disequilibrium structure and heterogeneity in allelic effects are expected to play a role in the associations observed between populations. Prior genome-wide association study (GWAS) meta-analyses have identified genomic loci associated with WBC and its subtypes, but much of the heritability of these phenotypes remains unexplained. Using GWAS summary statistics for over 50 000 individuals from three diverse populations (Japanese, African-American and European ancestry), a Bayesian model methodology was employed to account for heterogeneity between ancestry groups. This approach was used to perform a trans-ethnic meta-analysis of total WBC, neutrophil and monocyte counts. Ten previously known associations were replicated and six new loci were identified, including several regions harboring genes related to inflammation and immune cell function. Ninety-five percent credible interval regions were calculated to narrow the association signals and fine-map the putatively causal variants within loci. Finally, a conditional analysis was performed on the most significant SNPs identified by the trans-ethnic meta-analysis (MA), and nine secondary signals within loci previously associated with WBC or its subtypes were identified. This work illustrates the potential of trans-ethnic analysis and ascribes a critical role to multi-ethnic cohorts and consortia in exploring complex phenotypes with respect to variants that lie outside the European-biased GWAS pool.

AB - White blood cell (WBC) count is a common clinical measure used as a predictor of certain aspects of human health, including immunity and infection status. WBC count is also a complex trait that varies among individuals and ancestry groups. Differences in linkage disequilibrium structure and heterogeneity in allelic effects are expected to play a role in the associations observed between populations. Prior genome-wide association study (GWAS) meta-analyses have identified genomic loci associated with WBC and its subtypes, but much of the heritability of these phenotypes remains unexplained. Using GWAS summary statistics for over 50 000 individuals from three diverse populations (Japanese, African-American and European ancestry), a Bayesian model methodology was employed to account for heterogeneity between ancestry groups. This approach was used to perform a trans-ethnic meta-analysis of total WBC, neutrophil and monocyte counts. Ten previously known associations were replicated and six new loci were identified, including several regions harboring genes related to inflammation and immune cell function. Ninety-five percent credible interval regions were calculated to narrow the association signals and fine-map the putatively causal variants within loci. Finally, a conditional analysis was performed on the most significant SNPs identified by the trans-ethnic meta-analysis (MA), and nine secondary signals within loci previously associated with WBC or its subtypes were identified. This work illustrates the potential of trans-ethnic analysis and ascribes a critical role to multi-ethnic cohorts and consortia in exploring complex phenotypes with respect to variants that lie outside the European-biased GWAS pool.

UR - http://www.scopus.com/inward/record.url?scp=84951746884&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84951746884&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddu401

DO - 10.1093/hmg/ddu401

M3 - Article

VL - 23

SP - 6944

EP - 6960

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 25

ER -

CHARGE Hematology, COGENT, BioBank Japan Project (RIKEN) Working Groups. Trans-ethnic meta-analysis of white blood cell phenotypes. Human molecular genetics. 2014 12 20;23(25):6944-6960. https://doi.org/10.1093/hmg/ddu401