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Association Between Absolute Neutrophil Count and Variation at TCIRG1 : The NHLBI Exome Sequencing Project
Author(s) -
Rosenthal Elisabeth A.,
Makaryan Vahagn,
Burt Amber A.,
Crosslin David R.,
Kim Daniel Seung,
Smith Joshua D.,
Nickerson Deborah A.,
Reiner Alex P.,
Rich Stephen S.,
Jackson Rebecca D.,
Ganesh Santhi K.,
Polfus Linda M.,
Qi Lihong,
Dale David C.,
Jarvik Gail P.
Publication year - 2016
Publication title -
genetic epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.301
H-Index - 98
eISSN - 1098-2272
pISSN - 0741-0395
DOI - 10.1002/gepi.21976
Subject(s) - absolute neutrophil count , missense mutation , exome sequencing , medicine , biology , neutropenia , genetics , gene , mutation , toxicity
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.