TY  - JOUR
PY  - 2019//
TI  - Major depressive disorder-associated SIRT1 locus affects the risk for suicide in women after middle age
JO  - Psychiatry research
A1  - Hirata, Takashi
A1  - Otsuka, Ikuo
A1  - Okazaki, Satoshi
A1  - Mouri, Kentaro
A1  - Horai, Tadasu
A1  - Boku, Shuken
A1  - Takahashi, Motonori
A1  - Ueno, Yasuhiro
A1  - Sora, Ichiro
A1  - Shirakawa, Osamu
A1  - Hishimoto, Akitoyo
SP  - 141
EP  - 145
VL  - 278
IS  - 
N2  - 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.<br><br>Copyright © 2019 Elsevier B.V. All rights reserved.<p />  <p>Language: en</p>
LA  - en
SN  - 0165-1781
UR  - http://dx.doi.org/10.1016/j.psychres.2019.06.002
ID  - ref1
ER  -