Our previous genome-wide association study (CONVERGE sample) identified significant association between single nucleotide polymorphisms (SNPs) near the SIRT1 gene and major depressive disorder (MDD) in Chinese populations.

To investigate whether SNPs across the SIRT1 gene locus affect regional grey matter density in the Han Chinese population.

T1-weighted structural magnetic resonance imaging was conducted on 92 healthy participants from Eastern China. Grey matter was segmented from the image, which consisted of voxel-wise grey matter density. The effect of SIRT1 SNPs on grey matter density was determined by a multiple linear regression framework.

SNP rs4746720 was significantly associated with grey matter density in two brain cortical regions: the orbital part of the right inferior frontal gyrus and the orbital part of the left inferior frontal gyrus (family-wise error-corrected P < 0.05; voxel-wise P < 0.001). Also, rs4746720 exceeded genome-wide significance in association with MDD in our CONVERGE sample (P = 3.32 × 10−08, odds ratio 1.161).

Our results provided evidence for a potential role of the SIRT1 gene in the brain, implying a possible pathophysiological mechanism underlying susceptibility to MDD.