Genome-Wide Association Analysis of Soluble ICAM-1 Concentration Reveals Novel Associations at the NFKBIK, PNPLA3, RELA, and SH2B3 Loci

被引：74

作者：

Pare, Guillaume ^{[1
,2
,3
]}

Ridker, Paul M. ^{[1
,2
]}

Rose, Lynda ^{[1
,2
]}

Barbalic, Maja ^{[4
,5
]}

Dupuis, Josee ^{[6
,7
,8
]}

Dehghan, Abbas ^{[9
,10
]}

Bis, Joshua C. ^{[11
]}

Benjamin, Emelia J. ^{[6
,7
,12
,13
]}

Shiffman, Dov ^{[14
]}

Parker, Alexander N. ^{[15
]}

Chasman, Daniel I. ^{[1
,2
]}

机构：

[1] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Cardiovasc Dis Prevent, Boston, MA 02115 USA

[2] Harvard Univ, Brigham & Womens Hosp, Sch Med, Donald W Reynolds Ctr Cardiovasc Res, Boston, MA 02115 USA

[3] McMaster Univ, Hamilton, ON, Canada

[4] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA

[5] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX USA

[6] NHLBI, Framingham, MA USA

[7] Boston Univ, Framingham Heart Study, Framingham, MA USA

[8] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA

[9] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[10] NCHA, Leiden, Netherlands

[11] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA

[12] Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Dept Med, Boston, MA 02118 USA

[13] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA

[14] Celera, Alameda, CA USA

[15] Amgen Inc, Cambridge, MA USA

来源：

PLOS GENETICS | 2011年 / 7卷 / 04期

关键词：

INTERCELLULAR-ADHESION MOLECULE-1; NF-KAPPA-B; TRANSCRIPTIONAL REGULATION; CIRCULATING LEVELS; SEQUENCE VARIANTS; GENE; RISK; METAANALYSIS; SELECTIN; DISEASE;

D O I：

10.1371/journal.pgen.1001374

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Soluble ICAM-1 (sICAM-1) is an endothelium-derived inflammatory marker that has been associated with diverse conditions such as myocardial infarction, diabetes, stroke, and malaria. Despite evidence for a heritable component to sICAM-1 levels, few genetic loci have been identified so far. To comprehensively address this issue, we performed a genome-wide association analysis of sICAM-1 concentration in 22,435 apparently healthy women from the Women's Genome Health Study. While our results confirm the previously reported associations at the ABO and ICAM1 loci, four novel associations were identified in the vicinity of NFKBIK (rs3136642, P = 5.4x10(-9)), PNPLA3 (rs738409, P = 5.8x10(-9)), RELA (rs1049728, P = 2.7x10(-16)), and SH2B3 (rs3184504, P = 2.9x10(-17)). Two loci, NFKBIB and RELA, are involved in NFKB signaling pathway; PNPLA3 is known for its association with fatty liver disease; and SH3B2 has been associated with a multitude of traits and disease including myocardial infarction. These associations provide insights into the genetic regulation of sICAM-1 levels and implicate these loci in the regulation of endothelial function.

引用

页数：7

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