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Neuroticism is an important risk factor for psychiatric traits, including depression, anxiety^,, and schizophrenia^{, –}. At the time of analysis, previous genome-wide association studies^{, , , , –} (GWAS) reported 16 genomic loci associated to neuroticism^{, –}. Here we conducted a large GWAS meta-analysis (n = 449,484) of neuroticism and identified 136 independent genome-wide significant loci (124 new at the time of analysis), which implicate 599 genes. Functional follow-up analyses showed enrichment in several brain regions and involvement of specific cell types, including dopaminergic neuroblasts (P = 3.49 × 10⁻⁸), medium spiny neurons (P = 4.23 × 10⁻⁸), and serotonergic neurons (P = 1.37 × 10⁻⁷). Gene set analyses implicated three specific pathways: neurogenesis (P = 4.43 × 10⁻⁹), behavioral response to cocaine processes (P = 1.84 × 10⁻⁷), and axon part (P = 5.26 × 10⁻⁸). We …