A meta-analysis of 46 cohorts involving 611,037 to 1.14 million participants identified 1,260 lead genetic variants associated with the Big Five personality traits, including 824 in previously unlinked genomic regions. The associations were broadly consistent across cohorts and measurement contexts, while polygenic analyses linked personality-related genetics to health, behavior, psychopathology, and life outcomes, although effects were modest and could not predict individual behavior.