Figure 4.

Observed and genetic coronary heart disease risk (95% confidence intervals) per usual standard deviation higher adiposity measure among men and women combined. Observational analyses were restricted to 456 495 participants without outlying/missing adiposity variables or a history of cardiovascular disease at baseline. Genetic analyses were restricted to unrelated 369 225 participants of European ancestry, with complete genetic information, and without outlying/missing adiposity variables or a history of cardiovascular disease at baseline. Observational estimates were adjusted for age at baseline, ethnicity, education, region, smoking and alcohol. Genetic risk scores were composed of single-nucleotide polymorphisms (SNPs) discovered in European populations by using the GIANT consortia at genome-wide significance (P=5×10^–8). All SNPs were weighted by the effect size as estimated in the GIANT consortia. Genetic analyses include also multivariable Mendelian randomization and were stratified by age at risk and region, and adjusted for age at baseline (5-year groups), age,² sex, the first 10 genetic principle components, batch number and array type. The area of each box is proportional to the amount of statistical information (i.e. it is inversely proportional to the variance of the log-HR). GRS, genetic risk score; GRS-BMI, genetic risk score for body mass index; GRS-HC, genetic risk score for hip circumference; GRS-WHR, genetic risk score for waist-to-hip ratio; GRS-WC, genetic risk score for waist circumference; HR, hazard ratio