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Chunk #34 — Discussion

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Genome-wide association uncovers shared genetic effects among personality traits and mood states.
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The gene-based test identified six genes associated with neuroticism. Five (C15orf17, MPI, SCAMP2, ULK3, COX5A) were located in a region of tight LD, which was replicated in the Australian cohort. SNPs in ULK3 and SCAMP2 passed suggestive significance in the GWAS—and one in SCAMP2 was significant (albeit in the opposite direction) in the Australian cohort. SCAMP2 (secretory carrier membrane protein 2) was an interesting candidate because SCAMP2 plays a role in plasmalemmal norepinephrine transporter function, a drug target of mood disorder (Matthies et al. 2009). While not reaching corrected significance, NDE1 (nudE nuclear distribution gene E homolog 1) was nominally associated with symptoms of depression, and has been related to major depression. This gene encodes a protein involved in microtubal organisation, mitosis and neuronal migration. Variants in NDE1 affect expression levels of genes targeted by drugs for bipolar disorder and major depression (Hennah and Porteous 2009). There was good agreement between the top SNP associations (i.e., those located in genes) and the gene-based tests. That FHIT and RAVER1 were not significant in the gene-based test indicates that the SNP associations