Genetic variants associated with the white blood cell count in 13,923 subjects in the eMERGE Network

被引：88

作者：

Crosslin, David R. ^{[1
,2
]}

McDavid, Andrew ^{[3
]}

Weston, Noah ^{[4
]}

Nelson, Sarah C. ^{[1
]}

Zheng, Xiuwen ^{[1
]}

Hart, Eugene ^{[4
]}

de Andrade, Mariza ^{[5
]}

Kullo, Iftikhar J. ^{[6
]}

McCarty, Catherine A. ^{[7
]}

Doheny, Kimberly F. ^{[8
]}

Pugh, Elizabeth ^{[8
]}

Kho, Abel ^{[9
,10
]}

Hayes, M. Geoffrey ^{[11
]}

Pretel, Stephanie ^{[12
]}

Saip, Alexander ^{[13
]}

Ritchie, Marylyn D. ^{[14
]}

Crawford, Dana C. ^{[15
,16
]}

Crane, Paul K. ^{[17
]}

Newton, Katherine ^{[4
]}

Li, Rongling ^{[18
]}

Mirel, Daniel B. ^{[19
]}

Crenshaw, Andrew ^{[19
]}

Larson, Eric B. ^{[4
]}

Carlson, Chris S. ^{[3
]}

Jarvik, Gail P. ^{[2
]}

机构：

[1] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

[2] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA

[3] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA

[4] Grp Hlth Res Inst, Seattle, WA 98124 USA

[5] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN 55905 USA

[6] Mayo Clin, Div Cardiovasc Dis, Rochester, MN 55905 USA

[7] Essentia Inst Rural Hlth, Duluth, MN 55805 USA

[8] Johns Hopkins Univ, Ctr Inherited Dis Res, Baltimore, MD 21224 USA

[9] Northwestern Univ, Div Gen Internal Med, Chicago, IL 60611 USA

[10] Northwestern Univ, Div Hlth & Biomed Informat, Chicago, IL 60611 USA

[11] Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Chicago, IL 60611 USA

[12] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA

[13] Vanderbilt Univ, Vanderbilt Inst Clin & Translat Res, Nashville, TN 37232 USA

[14] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA

[15] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA

[16] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN 37232 USA

[17] Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA 98195 USA

[18] NHGRI, Off Populat Genom, NIH, Bethesda, MD 20892 USA

[19] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA

来源：

HUMAN GENETICS | 2012年 / 131卷 / 04期

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; CORONARY-HEART-DISEASE; LARGE-SCALE; RISK; LOCI; SUSCEPTIBILITY; ASTHMA; COMMON; AGE;

D O I：

10.1007/s00439-011-1103-9

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

White blood cell count (WBC) is unique among identified inflammatory predictors of chronic disease in that it is routinely measured in asymptomatic patients in the course of routine patient care. We led a genome-wide association analysis to identify variants associated with WBC levels in 13,923 subjects in the electronic Medical Records and Genomics (eMERGE) Network. We identified two regions of interest that were each unique to subjects of genetically determined ancestry to the African continent (AA) or to the European continent (EA). WBC varies among different ancestry groups. Despite being ancestry specific, these regions were identifiable in the combined analysis. In AA subjects, the region surrounding the Duffy antigen/chemokine receptor gene (DARC) on 1q21 exhibited significant association (p value = 6.71e-55). These results validate the previously reported association between WBC and of the regulatory variant rs2814778 in the promoter region, which causes the Duffy negative phenotype (Fy-/-). A second missense variant (rs12075) is responsible for the two principal antigens, Fya and Fyb of the Duffy blood group system. The two variants, consisting of four alleles, act in concert to produce five antigens and subsequent phenotypes. We were able to identify the marginal and novel interaction effects of these two variants on WBC. In the EA subjects, we identified significantly associated SNPs tagging three separate genes in the 17q21 region: (1) GSDMA, (2) MED24, and (3) PSMD3. Variants in this region have been reported to be associated with WBC, neutrophil count, and inflammatory diseases including asthma and Crohn's disease.

引用

页码：639 / 652

页数：14

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