Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Sep;40(6):470-4.
doi: 10.1002/gepi.21976. Epub 2016 May 27.

Association Between Absolute Neutrophil Count and Variation at TCIRG1: The NHLBI Exome Sequencing Project

Elisabeth A Rosenthal  1 , Vahagn Makaryan  2 , Amber A Burt  1 , David R Crosslin  3 , Daniel Seung Kim  3 , Joshua D Smith  3 , Deborah A Nickerson  3 , Alex P Reiner  4 , Stephen S Rich  5 , Rebecca D Jackson  6 , Santhi K Ganesh  7   8 , Linda M Polfus  9 , Lihong Qi  10 , David C Dale  2 ; University of Washington, Center for Mendelian Genomics; Gail P Jarvik  1   3
Affiliations

Association Between Absolute Neutrophil Count and Variation at TCIRG1: The NHLBI Exome Sequencing Project

Elisabeth A Rosenthal et al. Genet Epidemiol. 2016 Sep.

Abstract

Neutrophils are a key component of innate immunity. Individuals with low neutrophil count are susceptible to frequent infections. Linkage and association between congenital neutropenia and a single rare missense variant in TCIRG1 have been reported in a single family. Here, we report on nine rare missense variants at evolutionarily conserved sites in TCIRG1 that are associated with lower absolute neutrophil count (ANC; p = 0.005) in 1,058 participants from three cohorts: Atherosclerosis Risk in Communities (ARIC), Coronary Artery Risk Development in Young Adults (CARDIA), and Jackson Heart Study (JHS) of the NHLBI Grand Opportunity Exome Sequencing Project (GO ESP). These results validate the effects of TCIRG1 coding variation on ANC and suggest that this gene may be associated with a spectrum of mild to severe effects on ANC.

Keywords: absolute neutrophil count; neutropenia; next-generation sequence data; rare variant replication.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Boxplots of adjusted absolute neutrophil count (ANCadj) by TCIRG1 carrier status. The solid horizontal line in each boxplot is the median ANCadj for that group. The boundaries of each box extend to the interquartile range. The whiskers extend to 1.5 times the 25th and 75th percentiles. The widths of the boxes correspond to the sample size.
See this image and copyright information in PMC

References

    1. The atherosclerosis risk in communities (ARIC) study: Design and objectives. the ARIC investigators American Journal of Epidemiology. 1989 Apr;129(4):687–702. - PubMed
    1. Ancliff PJ, Blundell MP, Cory GO, Calle Y, Worth A, Kempski H, Burns S, et al. Two novel activating mutations in the wiskott-aldrich syndrome protein result in congenital neutropenia. Blood. 2006 Oct 1;108(7):2182–9. - PubMed
    1. Cooper GM, Stone EA, Asimenos G, NISC Comparative Sequencing Program. Green ED, Batzoglou S, Sidow A. Distribution and intensity of constraint in mammalian genomic sequence. Genome Research. 2005 Jul;15(7):901–13. - PMC - PubMed
    1. Crosslin DR, McDavid A, Weston N, Nelson SC, Zheng X, Hart E, de Andrade M, et al. Genetic variants associated with the white blood cell count in 13,923 subjects in the eMERGE network. Human Genetics. 2012 Apr;131(4):639–52. - PMC - PubMed
    1. Dale DC, Cottle TE, Fier CJ, Bolyard AA, Bonilla MA, Boxer LA, Cham B, et al. Severe chronic neutropenia: Treatment and follow-up of patients in the severe chronic neutropenia international registry. American Journal of Hematology. 2003 Feb;72(2):82–93. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources