Thus, our objective was to identify key aspects of body size over the life-course (since adolescence) that are associated with risk of the most commonly diagnosed breast cancers (i.e., those that are estrogen-receptor-positive (ER+)), jointly considering aspects of absolute obesity and stature, changes in adiposity over time, and body fat distributions using data from our large, diverse cohort of women prospectively followed for more than 10 years. The gene discussed is ESR1; the disease is obesity due to melanocortin 4 receptor deficiency.