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

Thursday,2014-05-29 13:02 America/Los_Angeles — poolea2
TitleMultiancestral analysis of inflammation-related genetic variants and C-reactive protein in the population architecture using genomics and epidemiology study.
Publication TypeJournal Article
Year of Publication2014
AuthorsKocarnik, JM, Pendergrass, SA, Carty, CL, Pankow, JS, Schumacher, FR, Cheng, I, Durda, P, Ambite, JLuis, Deelman, E, Cook, NR, Liu, S, Wactawski-Wende, J, Hutter, C, Brown-Gentry, K, Wilson, S, Best, LG, Pankratz, N, Hong, C-P, Cole, SA, V Voruganti, S, Bůzková, P, Jorgensen, NW, Jenny, NS, Wilkens, LR, Haiman, CA, Kolonel, LN, LaCroix, A, North, K, Jackson, R, Le Marchand, L, Hindorff, LA, Crawford, DC, Gross, M, Peters, U
JournalCirc Cardiovasc Genet
Volume7
Issue2
Pagination178-88
Date Published2014 Apr
ISSN1942-3268
KeywordsAdult, African Continental Ancestry Group, Aged, Asian Continental Ancestry Group, C-Reactive Protein, Female, Genetic Variation, Genome-Wide Association Study, Hispanic Americans, Humans, Indians, North American, Inflammation, Male, Middle Aged, Polymorphism, Single Nucleotide, United States, Young Adult
Abstract<p><b>BACKGROUND: </b>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.</p><p><b>METHODS AND RESULTS: </b>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)).</p><p><b>CONCLUSIONS: </b>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.</p>
DOI10.1161/CIRCGENETICS.113.000173
Alternate JournalCirc Cardiovasc Genet
PubMed ID24622110
PubMed Central IDPMC4104750
Grant ListN01HC55020 / HL / NHLBI NIH HHS / United States
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