Cohort profile: the 100 million Brazilian cohort

The creation of The 100 Million Brazilian Cohort was motivated by the availability of high quality but dispersed social and health databases in Brazil and the need to integrate data and evaluate the impact of policies aiming to improve the social determinants of health (e.g. social protection policies) on health outcomes, overall and in subgroups of interest in a dynamic cohort. • The baseline of The 100 Million Brazilian Cohort comprises 131 697 800 low-income individuals in 35 358 415 families from 2011 to 2018. The Cohort population is mostly composed of children and young adults, with a higher proportion of females than the general Brazilian population, who identify themselves as Brown and live in the urban area of the country. • Exposure to social protection and the follow-up of individuals are obtained through: (i) deterministic linkage using the Social Identification Number (NIS) to link the Cohort baseline to social protection programmes and to periodically renewed socioeconomic information in Cadatro U ́ nico datasets; and/or (ii) non-deterministic linkage using the CIDACS-RL non-deterministic linkage tool, to link the Cohort baseline to administrative health care datasets such as mortality (Mortality Information System, SIM), disease notification (Information System for Notifiable Diseases, SINAN), birth information (Live Birth Information System, SINASC) and nutrition status (Food and Nutrition Surveillance System, SISVAN). • So far, studies have used The 100 Million Brazilian Cohort to investigate the socioeconomic and demographic determinants of leprosy, leprosy treatment outcomes and low birthweight and to evaluate the impact of the Bolsa Familia Programme (BFP) on leprosy and child mortality. Other studies are now being conducted that are of utmost relevance to the health inequalities of Brazil and many low- and middle-income countries, and many research opportunities are being opened up with the linkage of a range of health outcomes

Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders

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 &lt;5 x 10(-8)). 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.</p