Back to Search
Start Over
The depression GWAS risk allele predicts smaller cerebellar gray matter volume and reduced SIRT1 mRNA expression in Chinese population
- Source :
- Translational Psychiatry, Vol 9, Iss 1, Pp 1-11 (2019), Translational Psychiatry
- Publication Year :
- 2019
- Publisher :
- Nature Publishing Group, 2019.
-
Abstract
- Major depressive disorder (MDD) is recognized as a primary cause of disability worldwide, and effective management of this illness has been a great challenge. While genetic component is supposed to play pivotal roles in MDD pathogenesis, the genetic and phenotypic heterogeneity of the illness has hampered the discovery of its genetic determinants. In this study, in an independent Han Chinese sample (1824 MDD cases and 3031 controls), we conducted replication analyses of two genetic loci highlighted in a previous Chinese MDD genome-wide association study (GWAS), and confirmed the significant association of a single nucleotide polymorphism (SNP) rs12415800 near SIRT1. Subsequently, using hypothesis-free whole-brain analysis in two independent Han Chinese imaging samples, we found that individuals carrying the MDD risk allele of rs12415800 exhibited aberrant gray matter volume in the left posterior cerebellar lobe compared with those carrying the non-risk allele. Besides, in independent Han Chinese postmortem brain and peripheral blood samples, the MDD risk allele of rs12415800 predicted lower SIRT1 mRNA levels, which was consistent with the reduced expression of this gene in MDD patients compared with healthy subjects. These results provide further evidence for the involvement of SIRT1 in MDD, and suggest that this gene might participate in the illness via affecting the development of cerebellum, a brain region that is potentially underestimated in previous MDD studies.
- Subjects :
- Adult
Male
China
Genome-wide association study
Single-nucleotide polymorphism
Bioinformatics
Polymorphism, Single Nucleotide
behavioral disciplines and activities
Article
lcsh:RC321-571
03 medical and health sciences
Cellular and Molecular Neuroscience
Young Adult
0302 clinical medicine
Sirtuin 1
mental disorders
medicine
SNP
Humans
RNA, Messenger
Allele
Young adult
Gray Matter
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
Biological Psychiatry
Alleles
030304 developmental biology
0303 health sciences
Depressive Disorder, Major
business.industry
Genetic heterogeneity
Depression
Case-control study
Genomics
Middle Aged
medicine.disease
Magnetic Resonance Imaging
3. Good health
Psychiatry and Mental health
Genetic Loci
Case-Control Studies
Major depressive disorder
Female
business
030217 neurology & neurosurgery
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- ISSN :
- 21583188
- Volume :
- 9
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Translational Psychiatry
- Accession number :
- edsair.doi.dedup.....e4880bc542418037ecf970cb0eca6f69