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

Pubmed ID: 27229898

Pubmed Central ID: PMC5079157

Journal: Genetic epidemiology

Publication Date: Sept. 1, 2016

MeSH Terms: Humans, Male, Adult, Female, Aged, Aged, 80 and over, United States, Alleles, Cohort Studies, Gene Frequency, Middle Aged, Genotype, Sequence Analysis, DNA, Leukocyte Count, National Heart, Lung, and Blood Institute (U.S.), Mutation, Missense, High-Throughput Nucleotide Sequencing, Neutropenia, Neutrophils, Vacuolar Proton-Translocating ATPases

Grants: RC2 HL102923, RC2 HL102926, RC2 HL102924, UM1 HG006493, RC2 HL103010, RC2 HL102925, U01 HG008657, R24 AI049393

Authors: Nickerson DA, Rosenthal EA, Makaryan V, Burt AA, Crosslin DR, Kim DS, Smith JD, Reiner AP, Rich SS, Jackson RD, Ganesh SK, Polfus LM, Qi L, Dale DC, Jarvik GP

Cite As: Rosenthal EA, Makaryan V, Burt AA, Crosslin DR, Kim DS, Smith JD, Nickerson DA, Reiner AP, Rich SS, Jackson RD, Ganesh SK, Polfus LM, Qi L, Dale DC, University of Washington Center for Mendelian Genomics, Jarvik GP. Association Between Absolute Neutrophil Count and Variation at TCIRG1: The NHLBI Exome Sequencing Project. Genet Epidemiol 2016 Sep;40(6):470-4. Epub 2016 May 27.

Studies:

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.