Meta-analysis of genome-wide association studies in >80 000 subjects identifies multiple loci for C-reactive protein levels.

TitleMeta-analysis of genome-wide association studies in >80 000 subjects identifies multiple loci for C-reactive protein levels.
Publication TypeJournal Article
Year of Publication2011
AuthorsDehghan A, Dupuis J, Barbalic M, Bis JC, Eiriksdottir G, Lu C, Pellikka N, Wallaschofski H, Kettunen J, Henneman P et al.
JournalCirculation
Volume123
Issue7
Pagination731-8
Date Published2011 Feb 22
ISSN1524-4539
KeywordsBiological Markers, C-Reactive Protein, Cardiovascular Diseases, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Risk Factors, Vasculitis
Abstract

BACKGROUND: C-reactive protein (CRP) is a heritable marker of chronic inflammation that is strongly associated with cardiovascular disease. We sought to identify genetic variants that are associated with CRP levels.

METHODS AND RESULTS: We performed a genome-wide association analysis of CRP in 66 185 participants from 15 population-based studies. We sought replication for the genome-wide significant and suggestive loci in a replication panel comprising 16 540 individuals from 10 independent studies. We found 18 genome-wide significant loci, and we provided evidence of replication for 8 of them. Our results confirm 7 previously known loci and introduce 11 novel loci that are implicated in pathways related to the metabolic syndrome (APOC1, HNF1A, LEPR, GCKR, HNF4A, and PTPN2) or the immune system (CRP, IL6R, NLRP3, IL1F10, and IRF1) or that reside in regions previously not known to play a role in chronic inflammation (PPP1R3B, SALL1, PABPC4, ASCL1, RORA, and BCL7B). We found a significant interaction of body mass index with LEPR (P<2.9×10(-6)). A weighted genetic risk score that was developed to summarize the effect of risk alleles was strongly associated with CRP levels and explained ≈5% of the trait variance; however, there was no evidence for these genetic variants explaining the association of CRP with coronary heart disease.

CONCLUSIONS: We identified 18 loci that were associated with CRP levels. Our study highlights immune response and metabolic regulatory pathways involved in the regulation of chronic inflammation.

DOI10.1161/CIRCULATIONAHA.110.948570
Alternate JournalCirculation
PubMed ID21300955