Bryan MS, et al. - Researchers performed gene-based tests using exome array data from 3479 women with breast cancer diagnosed before age 50 and 973 age-matched controls in order to determine loci associated with early-onset breast cancer. A population that developed breast cancer at all ages of onset was used to carry out replication. FGFR2, NEK10, and SIVA1 were three gene regions that were found to be associated with breast cancer incidence. Compared with a polygenic risk score, the performance of whole-genome prediction was better, and when combined with known epidemiologic risk factors, the AUC rose to 0.662. Overall, a role for variation within FGFR2 and NEK10 in breast cancer incidence was supported. SIVA1 was identified as a novel risk locus. Data indicated that women with early- and late-onset breast cancer share genetic etiology and risk assessment can be improved with whole-genome data.