首页 | 本学科首页   官方微博 | 高级检索  
     


Multiple loci are associated with white blood cell phenotypes
Authors:Nalls Michael A  Couper David J  Tanaka Toshiko  van Rooij Frank J A  Chen Ming-Huei  Smith Albert V  Toniolo Daniela  Zakai Neil A  Yang Qiong  Greinacher Andreas  Wood Andrew R  Garcia Melissa  Gasparini Paolo  Liu Yongmei  Lumley Thomas  Folsom Aaron R  Reiner Alex P  Gieger Christian  Lagou Vasiliki  Felix Janine F  Völzke Henry  Gouskova Natalia A  Biffi Alessandro  Döring Angela  Völker Uwe  Chong Sean  Wiggins Kerri L  Rendon Augusto  Dehghan Abbas  Moore Matt  Taylor Kent  Wilson James G  Lettre Guillaume  Hofman Albert  Bis Joshua C  Pirastu Nicola  Fox Caroline S  Meisinger Christa  Sambrook Jennifer  Arepalli Sampath
Affiliation:Laboratory of Neurogenetics, Intramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America. nallsm@mail.nih.gov
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.
Keywords:
本文献已被 PubMed 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号