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Multiancestral analysis of inflammation-related genetic variants and C-reactive protein in the population architecture using genomics and epidemiology study.

  • Author(s): Kocarnik, Jonathan M
  • Pendergrass, Sarah A
  • Carty, Cara L
  • Pankow, James S
  • Schumacher, Fredrick R
  • Cheng, Iona
  • Durda, Peter
  • Ambite, José Luis
  • Deelman, Ewa
  • Cook, Nancy R
  • Liu, Simin
  • Wactawski-Wende, Jean
  • Hutter, Carolyn
  • Brown-Gentry, Kristin
  • Wilson, Sarah
  • Best, Lyle G
  • Pankratz, Nathan
  • Hong, Ching-Ping
  • Cole, Shelley A
  • Voruganti, V Saroja
  • Bůžkova, Petra
  • Jorgensen, Neal W
  • Jenny, Nancy S
  • Wilkens, Lynne R
  • Haiman, Christopher A
  • Kolonel, Laurence N
  • Lacroix, Andrea
  • North, Kari
  • Jackson, Rebecca
  • Le Marchand, Loic
  • Hindorff, Lucia A
  • Crawford, Dana C
  • Gross, Myron
  • Peters, Ulrike
  • et al.

Published Web Location

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4104750/
No data is associated with this publication.
Abstract

BACKGROUND:C-reactive protein (CRP) is a biomarker of inflammation. Genome-wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs) associated with CRP concentrations and inflammation-related traits such as cardiovascular disease, type 2 diabetes mellitus, and obesity. We aimed to replicate previous CRP-SNP associations, assess whether these associations generalize to additional race/ethnicity groups, and evaluate inflammation-related SNPs for a potentially pleiotropic association with CRP. METHODS AND RESULTS:We selected and analyzed 16 CRP-associated and 250 inflammation-related GWAS SNPs among 40 473 African American, American Indian, Asian/Pacific Islander, European American, and Hispanic participants from 7 studies collaborating in the Population Architecture using Genomics and Epidemiology (PAGE) study. Fixed-effect meta-analyses combined study-specific race/ethnicity-stratified linear regression estimates to evaluate the association between each SNP and high-sensitivity CRP. Overall, 18 SNPs in 8 loci were significantly associated with CRP (Bonferroni-corrected P<3.1×10(-3) for replication, P<2.0×10(-4) for pleiotropy): Seven of these were specific to European Americans, while 9 additionally generalized to African Americans (1), Hispanics (5), or both (3); 1 SNP was seen only in African Americans and Hispanics. Two SNPs in the CELSR2/PSRC1/SORT1 locus showed a potentially novel association with CRP: rs599839 (P=2.0×10(-6)) and rs646776 (P=3.1×10(-5)). CONCLUSIONS:We replicated 16 SNP-CRP associations, 10 of which generalized to African Americans and/or Hispanics. We also identified potentially novel pleiotropic associations with CRP for two SNPs previously associated with coronary artery disease and/or low-density lipoprotein-cholesterol. These findings demonstrate the benefit of evaluating genotype-phenotype associations in multiple race/ethnicity groups and looking for pleiotropic relationships among SNPs previously associated with related phenotypes.

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