Genome-wide association studies reveal sex-biased obesity-risk loci: SAFB-like transcription modulator (SLTM) variants selectively increase male adiposity, whereas rare death inducer obliterator 1 (DIDO1) and SLC12A5 mutations exhibit female-specific associations with elevated body mass index (>80% penetrance in females). This evidence concerns the gene SLTM and obesity due to melanocortin 4 receptor deficiency.