Study Report
Reference
| Citation | Kohli MA, 2011 PubMed |
| Full Info | Kohli MA, Lucae S, Saemann PG, Schmidt MV, Demirkan A, Hek K et al. The neuronal transporter gene SLC6A15 confers risk to major depression. Neuron 2011; 70(2): 252-265.
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Study
| Hypothesis or Background |
Major depression (MD) is one of the most prevalent psychiatric disorders and a leading cause of loss in work productivity. A combination of genetic and environmental risk factors probably contributes to MD.
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| Sample Information | sample of MD inpatients of a tertiary clinic in Munich, Germany, and matched controls devoid of any life-time psychiatric diagnoses (n = 353/366) recruited for the Munich, animal model |
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| Method Detail | |
| Method Keywords | genotyping; magnetic resonance imaging (MRI) |
| Result | We present data from a genome-wide association study revealing a neuron-specific neutral amino acid transporter (SLC6A15) as a susceptibility gene for MD. Risk allele carrier status in humans and chronic stress in mice were associated with a downregulation of the expression of this gene in the hippocampus, a brain region implicated in the pathophysiology of MD. The same polymorphisms also showed associations with alterations in hippocampal volume and neuronal integrity. Thus, decreased SLC6A15 expression, due to genetic or environmental factors, might alter neuronal circuits related to the susceptibility for MD. |
| Conclusions | Our convergent data from human genetics, expression studies, brain imaging, and animal models suggest a pathophysiological mechanism for MD that may be accessible to drug targeting. |
Relationships reported by
Kohli MA, 2011
| Component A Approved Name (Name in Paper) |
Component A Type |
Component B Approved Name (Name in Paper) |
Component B Type |
Statistical Result |
Relationship Description |
Result Category (Positive/Negative)) |
|
SLC6A15 (SLC6A15)
|
gene |
rs1545843 (rs1545843) |
SNP |
p = 0.00043 |
The MD risk genotype (AA) is associated with reduced full-length SLC6A15 mRNA expression levels compared to the nonrisk genotypes (AG+GG). |
Positive
|
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MDD
|
syndrome |
rs1545843 (rs1545843) |
SNP |
p = 5.53e-08; OR = 2.84 [95% CI1.92¨C4.21]) |
The commonSNP rs1545843 (MAF = 0.41 in controls) on chr12q21.31 showedexperiment-wide signi?cance in a recessive mode of inheritance(AA versus AG+GG) after pplying the permutation-based minimum p method for multiple comparison correction over all tested SNPs and genetic models |
Positive
|
|
rs1545843 (rs1545843)
|
SNP |
Hippocampus (hippocampal volumes) |
brain morphology and function |
bilateral hippocampal volume (F>15.128, p<1.2e-04, N=204); left group: case- control, genotypes AA vs. AG/GG: F=5.861, P-value = 0.016, right: F=5.686, P-value = 0.018. |
We confirmed bilateral hippocampal volume reductions in recurrent depression (F>15.128, p<1.2e-04, N=204) and found a rs1545843 genotype diagnosis interaction effect on both left and right total hippocampal volumes¡£ |
Positive
|
