Abstract：
:A recent genome-wide association study (GWAS) for major depressive disorder (MDD) in Chinese women identified a single-nucleotide polymorphism (SNP), rs12415800, near the Sirtuin1 (SIRT1) gene as one of the top candidate loci. However, no study has shown a genetic association between SIRT1 and completed suicide, which is one of the most serious outcomes of MDD. In this study, 778 suicide completers and 760 controls in a Japanese population were genotyped for two SNPs in strong linkage disequilibrium (rs12415800 and rs4746720 in 3'UTR). We found significant associations between both SNPs and completed suicide among women aged ≥50 years. Additional analysis using postmortem brain tissues (10 suicide brains and 13 non-suicide brains) revealed the following: while SIRT1 gene expression in the prefrontal cortex did not differ between suicide and non-suicide brains, DNAJC12 gene expression, potentially implicated by the SNPs genotyped here, was significantly decreased in suicide brains (p = 0.003). In conclusion, regarding the genetic association of SIRT1 with MDD that was previously identified in women by the Chinese GWAS, we successfully validated our results using a female suicidal cohort in the same Asian population with the same direction of allelic effect.
journal_name
Psychiatry Resjournal_title
Psychiatry researchauthors
Hirata T,Otsuka I,Okazaki S,Mouri K,Horai T,Boku S,Takahashi M,Ueno Y,Sora I,Shirakawa O,Hishimoto Adoi
10.1016/j.psychres.2019.06.002subject
Has Abstractpub_date
2019-08-01 00:00:00pages
141-145eissn
0165-1781issn
1872-7123pii
S0165-1781(19)30380-4journal_volume
278pub_type
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