Multiancestral Analysis of Inflammation-Related Genetic Variants and C-Reactive Protein in the Population Architecture Using Genomics and Epidemiology Study

Media type: E-Article
Title: Multiancestral Analysis of Inflammation-Related Genetic Variants and C-Reactive Protein in the Population Architecture Using Genomics and Epidemiology Study
Contributor: 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; Bůžková, Petra; Jorgensen, Neal W.; Jenny, Nancy S.; Wilkens, Lynne R.; [...]
imprint: Ovid Technologies (Wolters Kluwer Health), 2014
Published in: Circulation: Cardiovascular Genetics
Language: English
DOI: 10.1161/circgenetics.113.000173
ISSN: 1942-325X; 1942-3268
Origination:
Footnote:
Description: <jats:sec> <jats:title>Background—</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods and Results—</jats:title> <jats:p> 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 <jats:italic>P</jats:italic> <3.1×10 <jats:sup>−3</jats:sup> for replication, <jats:italic>P</jats:italic> <2.0×10 <jats:sup>−4</jats:sup> 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 <jats:italic>CELSR2/PSRC1/SORT1</jats:italic> locus showed a potentially novel association with CRP: rs599839 ( <jats:italic>P</jats:italic> =2.0×10 <jats:sup>−6</jats:sup> ) and rs646776 ( <jats:italic>P</jats:italic> =3.1×10 <jats:sup>−5</jats:sup> ). </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions—</jats:title> <jats:p>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.</jats:p> </jats:sec>
Access State: Open Access

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