Back to Search Start Over

Multiple loci are associated with white blood cell phenotypes

Authors :
Jacqueline C.M. Witteman
Holger Prokisch
Nicole L. Glazer
Koichi Matsuda
André G. Uitterlinden
Christian Gieger
Vilmundur Gudnason
Neil A. Zakai
Kerri L. Wiggins
Ming-Huei Chen
Stephan Menzel
Eric Boerwinkle
Angela Döring
Toshiko Tanaka
Natalia Gouskova
Inga Prokopenko
Aravinda Chakravarti
Caroline S. Fox
Jing-Ping Lin
Nicole Soranzo
Henry Völzke
Matt Moore
Sean Chong
Gudny Eiriksdottir
Paolo Gasparini
Bruce M. Psaty
Uwe Völker
Christa Meisinger
Kushang V. Patel
Joshua C. Bis
Guillaume Lettre
Brigitte Kühnel
Ben A. Oostra
Vasiliki Lagou
Dena G. Hernandez
Albert V. Smith
Alexander Teumer
Janine F. Felix
Mike A. Nalls
Daniel Levy
Abbas Dehghan
Tamara B. Harris
Luigi Ferrucci
Andreas Greinacher
Alessandro Biffi
Jonathan Stephens
Michael Stumvoll
Daniela Toniolo
Toshihiro Tanaka
Massimo Mangino
Augusto Rendon
Willem H. Ouwehand
Santhi K. Ganesh
Anke Tönjes
Kazuhiko Yamamoto
Yusuke Nakamura
Tatsuhiko Tsunoda
Nicola Pirastu
Giorgio Pistis
Josef Coresh
Qiong Yang
Frank J. A. van Rooij
Jennifer G. Sambrook
Yoichiro Kamatani
James G. Wilson
Stefania Bandinelli
Kent D. Taylor
H.-Erich Wichmann
Dan L. Longo
Atsushi Takahashi
Michiaki Kubo
David Melzer
Thomas Lumley
David Couper
Yukinori Okada
Sampath Arepalli
Matthias Nauck
Thomas Illig
Aaron R. Folsom
Cornelia M. van Duijn
Stephen F. Garner
Albert Hofman
Andrew B. Singleton
Naoyuki Kamatani
Yongmei Liu
L. Adrienne Cupples
Christopher J. O'Donnell
Melissa E. Garcia
Alexander P. Reiner
Tim D. Spector
Andrew R. Wood
Swee Lay Thein
Timothy M. Frayling
Nalls, Ma
Couper, Dj
Tanaka, T
van Rooij, Fj
Chen, Mh
Smith, Av
Toniolo, D
Zakai, Na
Yang, Q
Greinacher, A
Wood, Ar
Garcia, M
Gasparini, Paolo
Liu, Y
Lumley, T
Folsom, Ar
Reiner, Ap
Gieger, C
Lagou, V
Felix, Jf
Völzke, H
Gouskova, Na
Biffi, A
Döring, A
Völker, U
Chong, S
Wiggins, Kl
Rendon, A
Dehghan, A
Moore, M
Taylor, K
Wilson, Jg
Lettre, G
Hofman, A
Bis, Jc
Pirastu, Nicola
Fox, C
Meisinger, C
Sambrook, J
Arepalli, S
Nauck, M
Prokisch, H
Stephens, J
Glazer, Nl
Cupples, La
Okada, Y
Takahashi, A
Kamatani, Y
Matsuda, K
Tsunoda, T
Kubo, M
Nakamura, Y
Yamamoto, K
Kamatani, N
Stumvoll, M
Tönjes, A
Prokopenko, I
Illig, T
Patel, Kv
Garner, Sf
Kuhnel, B
Mangino, M
Oostra, Ba
Thein, Sl
Coresh, J
Wichmann, He
Menzel, S
Lin, J
Pistis, G
Uitterlinden, Ag
Spector, Td
Teumer, A
Eiriksdottir, G
Gudnason, V
Bandinelli, S
Frayling, Tm
Chakravarti, A
van Duijn, Cm
Melzer, D
Ouwehand, Wh
Levy, D
Boerwinkle, E
Singleton, Ab
Hernandez, Dg
Longo, Dl
Soranzo, N
Witteman, Jc
Psaty, Bm
Ferrucci, L
Harris, Tb
O'Donnell, Cj
Ganesh, Sk
Source :
King's College London, e1002113, PLoS Genetics, Vol 7, Iss 6, p e1002113 (2011), PLoS Genetics; Vol 7, PLoS Genetics
Publication Year :
2011

Abstract

White blood cell (WBC) count is a common clinical measure from complete blood count assays, and it varies widely among healthy individuals. Total WBC count and its constituent subtypes have been shown to be moderately heritable, with the heritability estimates varying across cell types. We studied 19,509 subjects from seven cohorts in a discovery analysis, and 11,823 subjects from ten cohorts for replication analyses, to determine genetic factors influencing variability within the normal hematological range for total WBC count and five WBC subtype measures. Cohort specific data was supplied by the CHARGE, HeamGen, and INGI consortia, as well as independent collaborative studies. We identified and replicated ten associations with total WBC count and five WBC subtypes at seven different genomic loci (total WBC count-6p21 in the HLA region, 17q21 near ORMDL3, and CSF3; neutrophil count-17q21; basophil count-3p21 near RPN1 and C3orf27; lymphocyte count-6p21, 19p13 at EPS15L1; monocyte count-2q31 at ITGA4, 3q21, 8q24 an intergenic region, 9q31 near EDG2), including three previously reported associations and seven novel associations. To investigate functional relationships among variants contributing to variability in the six WBC traits, we utilized gene expression- and pathways-based analyses. We implemented gene-clustering algorithms to evaluate functional connectivity among implicated loci and showed functional relationships across cell types. Gene expression data from whole blood was utilized to show that significant biological consequences can be extracted from our genome-wide analyses, with effect estimates for significant loci from the meta-analyses being highly corellated with the proximal gene expression. In addition, collaborative efforts between the groups contributing to this study and related studies conducted by the COGENT and RIKEN groups allowed for the examination of effect homogeneity for genome-wide significant associations across populations of diverse ancestral backgrounds.

Details

Language :
English
Database :
OpenAIRE
Journal :
King's College London, e1002113, PLoS Genetics, Vol 7, Iss 6, p e1002113 (2011), PLoS Genetics; Vol 7, PLoS Genetics
Accession number :
edsair.doi.dedup.....4fe240d33e7ff06d82171527d2bc8eb2