Locus-specific differences in DNA replication timing have been associated with various genomic features, including altered mutation rates. To study the impact of genetic variation on genome-wide patterns of human DNA replication timing, Steve McCarroll and colleagues (Cell 159, 1015–1026, 2014) used a sequence-based approach to construct replication timing profiles for proliferating lymphoblastoid cell lines derived from 161 individuals from the 1000 Genomes Project. Overall, they identified 477 genomic regions exhibiting individual-level variation in DNA replication timing. They then tested whether variation in replication timing in these regions was associated with DNA sequence variation. Association analyses using the 161 discovery samples and an additional 334 independent samples identified 16 distinct genetic loci influencing DNA replication timing in cis. In addition, among the loci that fell just below the threshold for genome-wide significance, they observed a signal near JAK2 that coincided with a haplotype previously associated with predisposition to somatic JAK2 mutations and risk of myeloproliferative neoplasms. Notably, the haplotype associated with predisposition to somatic JAK2 mutations is associated with earlier replication timing, with the elevated mutation rate possibly driven by interference between the replication and transcription machineries.