Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, 474 potentially impacting the overall trait variance when investigating the genetic contribution to obesity-475 related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% 476 European descent) to identify loci influencing BMI and central adiposity, measured as waist 477 circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci 478 with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show 479 consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci 480 in an independent study sample. These loci highlight novel biological functions, including response to 481 oxidative stress, addictive behavior, and regulatory functions emphasizing the importance of accounting 482 for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic 483 susceptibility to overall adiposity and body fat distribution.