Of the SNPs that showed the strongest association with Neuroticism, rs362584 (P = 5.03 × 10−5) is attractive, because it is within intron 1 of the gene synaptosomal-associated protein of 25 kD (SNAP25). SNAP25 plays a critical role in neurotransmitter release, axonal growth, and synaptic plasticity (56). Deletion of the region containing the SNAP-25 gene in the Coloboma mouse causes neurological abnormalities, including hyperactivity. Such a phenotype is consistent with a role for SNAP25 in attention deficit hyperactivity disorder, which has been tested in a number of studies with mostly positive results (57, 58). Furthermore, abnormalities in the level of SNAP25 have been linked to other psychiatric disorders (59-61), and genetic variants in SNAP25 have been associated with cognitive ability (62). In addition to its intrinsic interest for a personality trait, the association between SNAP-25 and Neuroticism is relevant to several psychiatric disorders for which Neuroticism is an intermediate phenotype/endophenotype. In the follow-up samples we found a trend, in the same direction, for the association of SNAP25 with Neuroticism (P = .097). A SNP in the gene TMEM16D (rs1849710; P
