Differential Effects of Environmental and Genetic Factors on T and B Cell Immune Traits

被引：140

作者：

Aguirre-Gamboa, Raul ^{[1
]}

Joosten, Irma ^{[2
]}

Urbano, Paulo C. M. ^{[2
]}

van der Molen, Renate G. ^{[2
]}

van Rijssen, Esther ^{[2
]}

van Cranenbroek, Bram ^{[2
]}

Oosting, Marije ^{[3
,4
]}

Smeekens, Sanne ^{[3
,4
]}

Jaeger, Martin ^{[3
,4
]}

Zorro, Maria ^{[1
]}

Withoff, Sebo ^{[1
]}

van Herwaarden, Antonius E. ^{[5
]}

Sweep, Fred C. G. J. ^{[5
]}

Netea, Romana T. ^{[3
,4
]}

Swertz, Morris A. ^{[1
,6
]}

Franke, Lude ^{[1
]}

Xavier, Ramnik J. ^{[7
,8
,9
,10
]}

Joosten, Leo A. B. ^{[3
,4
]}

Netea, Mihai G. ^{[3
,4
]}

Wijmenga, Cisca ^{[1
,11
]}

Kumar, Vinod ^{[1
]}

Li, Yang ^{[1
]}

Koenen, Hans J. P. M. ^{[2
]}

机构：

[1] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9713 AV Groningen, Netherlands

[2] Radboud Univ Nijmegen, Med Ctr, Lab Med Immunol, Dept Lab Med, NL-6525 GA Nijmegen, Netherlands

[3] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, NL-6525 GA Nijmegen, Netherlands

[4] Radboud Univ Nijmegen, Med Ctr, Radboud Ctr Infect Dis, NL-6525 GA Nijmegen, Netherlands

[5] Radboud Univ Nijmegen, Med Ctr, Clin Chem Lab, Dept Lab Med, NL-6525 GA Nijmegen, Netherlands

[6] Univ Groningen, Univ Med Ctr Groningen, Genom Coordinat Ctr, NL-9713 AV Groningen, Netherlands

[7] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA

[8] Harvard Sch Med, Boston, MA 02114 USA

[9] MIT, Broad Inst, Cambridge, MA 02142 USA

[10] Harvard Univ, Cambridge, MA 02142 USA

[11] Univ Oslo, Oslo Univ Hosp, Rikshosp, Dept Immunol, N-0372 Oslo, Norway

来源：

CELL REPORTS | 2016年 / 17卷 / 09期

基金：

欧洲研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; IMMUNOGLOBULIN PRODUCTION; EXPRESSION ANALYSIS; CYTOKINE PRODUCTION; AGE; INNATE; SYSTEM; HERITABILITY;

D O I：

10.1016/j.celrep.2016.10.053

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Effective immunity requires a complex network of cellular and humoral components that interact with each other and are influenced by different environmental and host factors. We used a systems biology approach to comprehensively assess the impact of environmental and genetic factors on immune cell populations in peripheral blood, including associations with immunoglobulin concentrations, from similar to 500 healthy volunteers from the Human Functional Genomics Project. Genetic heritability estimation showed that variations in T cell numbers are more strongly driven by genetic factors, while B cell counts are more environmentally influenced. Quantitative trait loci (QTL) mapping identified eight independent genomic loci associated with leukocyte count variation, including four associations with T and B cell subtypes. The QTLs identified were enriched among genome-wide association study (GWAS) SNPs reported to increase susceptibility to immune-mediated diseases. Our systems approach provides insights into cellular and humoral immune trait variability in humans.

引用

页码：2474 / 2487

页数：14

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