Association between C reactive protein and coronary heart disease: mendelian randomisation analysis based on individual participant data

• Published in: BMJ 2011-02, Vol.342 (77994), p.425-425
• Main Authors: Wensley, Frances, Gao, Pei, Burgess, Stephen, Kaptoge, Stephen, Di Angelantonio, Emanuele, Shah, Tina, Engert, James C, Clarke, Robert, Davey-Smith, George, Nordestgaard, Børge G, Saleheen, Danish, Samani, Nilesh J, Sandhu, Manjinder, Anand, Sonia, Pepys, Mark B, Smeeth, Liam, Whittaker, John, Casas, Juan Pablo, Thompson, Simon G, Hingorani, Aroon D, Danesh, John
• Format: Article
• Language: English
• Subjects: Alleles; C-reactive protein; C-Reactive Protein - genetics; C-Reactive Protein - metabolism; Cardiovascular disease; Causality; Collaboration; Concentration; Coronary artery disease; Coronary Disease - blood; Coronary Disease - genetics; Coronary diseases; Disease risk; Drugs: Cardiovascular System; Female; Gene Frequency; Genetic markers; Health risk assessment; Heart diseases; Humans; Ischaemic Heart Disease; Low density lipoprotein; Male; Medical genetics; Mendelian Randomization Analysis; Meta-analysis; Middle Aged; Molecular Genetics; Polymorphism, Single Nucleotide - genetics; Predisposing factors; Prospective Studies; Proteins; RecA protein; Risk Factors; Single-nucleotide polymorphism; Variants
• ISSN: 0959-8138; 0959-8146; 0959-535X; 1756-1833; 1468-5833; 1756-1833
• DOI: 10.1136/bmj.d548

Objective To use genetic variants as unconfounded proxies of C reactive protein concentration to study its causal role in coronary heart disease.Design Mendelian randomisation meta-analysis of individual participant data from 47 epidemiological studies in 15 countries.Participants 194 418 participants, including 46 557 patients with prevalent or incident coronary heart disease. Information was available on four CRP gene tagging single nucleotide polymorphisms (rs3093077, rs1205, rs1130864, rs1800947), concentration of C reactive protein, and levels of other risk factors.Main outcome measures Risk ratios for coronary heart disease associated with genetically raised C reactive protein versus risk ratios with equivalent differences in C reactive protein concentration itself, adjusted for conventional risk factors and variability in risk factor levels within individuals.Results CRP variants were each associated with up to 30% per allele difference in concentration of C reactive protein (P