title: Association Between Absolute Neutrophil Count and Variation at TCIRG1: The NHLBI Exome Sequencing Project.
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.
authors.affiliation: Division of Medical Genetics, School of Medicine, University of Washington, Seattle, Washington, United States of America.
authors.forename: Elisabeth A
authors.initials: EA
authors.lastname: Rosenthal
authors.affiliation: Division of General Internal Medicine, School of Medicine, University of Washington, Seattle, Washington, United States of America.
authors.forename: Vahagn
authors.initials: V
authors.lastname: Makaryan
authors.affiliation: Division of Medical Genetics, School of Medicine, University of Washington, Seattle, Washington, United States of America.
authors.forename: Amber A
authors.initials: AA
authors.lastname: Burt
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America.
authors.forename: David R
authors.initials: DR
authors.lastname: Crosslin
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America.
authors.forename: Daniel Seung
authors.initials: DS
authors.lastname: Kim
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Smith
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Nickerson
authors.affiliation: Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington, United States of America.
authors.forename: Alex P
authors.initials: AP
authors.lastname: Reiner
authors.affiliation: Center for Public Health Genomics, School of Medicine, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Rebecca D
authors.initials: RD
authors.lastname: Jackson
authors.affiliation: Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.|Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
authors.forename: Santhi K
authors.initials: SK
authors.lastname: Ganesh
authors.affiliation: Human Genetics Center, University of Texas Health Science Center, Houston, Texas, United States of America.
authors.forename: Linda M
authors.initials: LM
authors.lastname: Polfus
authors.affiliation: Division of Biostatistics, Department of Public Health Sciences, School of Medicine, University of California, Davis, California, United States of America.
authors.forename: Lihong
authors.initials: L
authors.lastname: Qi
authors.affiliation: Division of General Internal Medicine, School of Medicine, University of Washington, Seattle, Washington, United States of America.
authors.forename: David C
authors.initials: DC
authors.lastname: Dale
authors.affiliation: Division of Medical Genetics, School of Medicine, University of Washington, Seattle, Washington, United States of America.|Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America.
authors.forename: Gail P
authors.initials: GP
authors.lastname: Jarvik
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D054555:National Heart, Lung, and Blood Institute (U.S.); D009503:Neutropenia / Q000235:genetics* / Q000473:pathology; D009504:Neutrophils / Q000166:cytology*; D017422:Sequence Analysis, DNA; D014481:United States; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics*
chemical_list: C472421:TCIRG1 protein, human; D025262:Vacuolar Proton-Translocating ATPases
keywords: absolute neutrophil count; neutropenia; next-generation sequence data; rare variant replication