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

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

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


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 inflammationrelated 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 metaanalyses 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 (Bonferronicorrected 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.

Original languageEnglish (US)
Pages (from-to)178-188
Number of pages11
JournalCirculation: Cardiovascular Genetics
Issue number2
StatePublished - Apr 2014


  • C-reactive protein
  • Continental population groups
  • Ethnic groups
  • Genetic pleiotropy
  • Inflammation
  • Molecular epidemiology
  • Polymorphism
  • Single nucleotide

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