title: Genome-wide association study for C-reactive protein levels identified pleiotropic associations in the IL6 locus.
abstract: C-reactive protein (CRP) is a hallmark acute-phase reactant and is widely used as a blood marker for inflammation. Substantial roles of serum CRP levels in the pathogenesis of diseases have been suggested, and investigation of the mechanisms that regulate serum CRP levels would have a substantial clinical impact. Here, through genome-wide association and replication studies performed using 12 854 Japanese subjects, we identified a significant association between serum CRP levels and a single nucleotide polymorphism in the promoter region of interleukin-6 (IL6) (rs2097677, P = 4.1 × 10(-11)), a typical pleiotropic pro-inflammatory cytokine. Our study also replicated the associations in the CRP (rs3093059, P = 3.5 × 10(-21)) and HNF1A loci (rs7310409, P = 2.7 × 10(-8)). Pleiotropic association analysis with hematological and biochemical traits using 30 466 Japanese subjects demonstrated that the CRP-increasing allele of rs2097677 in the IL6 locus was significantly associated with an increased white blood cell count, platelet count and serum globulin and a decreased mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration (P < 5.0 × 10(-4)), although no pleiotropic association was observed in the CRP or HNF1A locus (α = 0.01). Our study demonstrated the pivotal role of the IL6 locus in the regulation of serum CRP levels and inflammatory pathways.
authors.affiliation: Laboratory for Statistical Analysis, Center for Genomic Medicine, RIKEN, Yokohama, Japan. yokada@src.riken.jp
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Okada
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takahashi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ohmiya
authors.forename: Natsuhiko
authors.initials: N
authors.lastname: Kumasaka
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Kamatani
authors.forename: Naoya
authors.initials: N
authors.lastname: Hosono
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Tsunoda
authors.forename: Koichi
authors.initials: K
authors.lastname: Matsuda
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tanaka
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D002097:C-Reactive Protein / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D015850:Interleukin-6; D002097:C-Reactive Protein