Variants were prioritized for further evaluation by allele frequency in one or more ancestral group (MAF > 10%), potential function using in silico prediction models, location near a known GWAS hit for breast cancer or related phenotype (e.g., age of menarche, obesity), location near a gene involved in tumor development, or known relationship to TP53 or PI3K pathways (Fig. 1A and B; Supplementary Tables S6 and S17). The gene discussed is PIK3CA; the disease is obesity due to melanocortin 4 receptor deficiency.