The meta-analysis of GWA results for neuroticism showed a genome-wide significant SNP in an intron of the MAGI1 gene. The MAGI1 gene is expressed in neuronal tissue, in particular the hippocampus, and is found at the synaptic plasma membrane.52 In addition, it has been shown that MAGI1 acts as a scaffolding protein in the neurite growth factor (NGF) receptor-mediated signaling pathway.53 Interestingly, the MAGI1 gene has previously been implicated in bipolar disorder, schizophrenia and episodicity in MDD54–56, disorders that in part share their genetic etiology.57 A genome-wide linkage scan for early onset bipolar disorder type 1 revealed genome-wide significant linkage in the 3p14 region where MAGI1 is located.56 A copy number variation study found evidence for deletions in MAGI1 to be associated with bipolar disorder and duplications to be associated with schizophrenia.54 Further, a genome-wide association study found suggestive association (P=5.1 × 10−7) of a SNP in MAGI1 with episodicity in MDD, a feature of MDD that shows increased risk to shifting to bipolar disorder.55
