C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 3 10 À8). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences.

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Objectives: To compare a widely used Australian food-frequency questionnaire (FFQ) with diet records and consider the results in relation to its use in nutrition surveillance. Design: Inter-method reliability study. Setting: A randomised trial in subjects with past asbestos exposure. Subjects: Seventy-two adults living in Western Australia. Methods: A semi-quantitative FFQ developed by the Commonwealth Scientific Industrial Research Organisation in South Australia was administered after the completion of four 7-day diet records (DRs). Results: Mean agreement between methods was not significantly different from 100% for many nutrients, but the limits of agreement indicated that, at the individual level, the FFQ over-or underestimated the DR by at least 50%. Mean agreement between methods decreased significantly with increasing intakes for the majority of nutrients. Pearson's correlation coefficients were less informative indicators of agreement compared with the limits of agreement. Conclusions: These results indicate poor agreement between the FFQ and DR when estimating absolute intakes. Therefore, comparing intakes collected using this FFQ with specific cut-off points such as Recommended Dietary Intakes for nutrition surveillance may lead to seriously flawed conclusions about population intakes.