Study Report
Reference
| Citation | Rietschel, 2010 PubMed |
| Full Info | Rietschel, M., Mattheisen, M., Frank, J., Treutlein, J., Degenhardt, F., Breuer, R., Steffens, M., Mier, D., Esslinger, C., Walter, H. et al. (2010) Genome-wide association-, replication-, and neuroimaging study implicates HOMER1 in the etiology of major depression. Biol Psychiatry, 68, 578-585.
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Study
| Hypothesis or Background |
Genome-wide association studies are a powerful tool for unravelling the genetic background of complex disorders such as major depression.
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| Sample Information | 604 patients with major depression and 1364 population based control subjects; 409 patients and 541 control subjects |
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| Method Detail | We conducted a genome-wide association study of 604 patients with major depression and 1364 population based control subjects. The top hundred findings were followed up in a replication sample of 409 patients and 541 control subjects. |
| Method Keywords | genotyping |
| Result | Two SNPs showed nominally significant association in both the genome-wide association study and the replication samples: 1) rs9943849 (p(combined) = 3.24E-6) located upstream of the carboxypeptidase M (CPM) gene and 2) rs7713917 (p(combined) = 1.48E-6), located in a putative regulatory region of HOMER1. Further evidence for HOMER1 was obtained through gene-wide analysis while conditioning on the genotypes of rs7713917 (p(combined) = 4.12E-3). Homer1 knockout mice display behavioral traits that are paradigmatic of depression, and transcriptional variants of Homer1 result in the dysregulation of cortical-limbic circuitry. This is consistent with the findings of our subsequent human imaging genetics study, which revealed that variation in single nucleotide polymorphism rs7713917 had a significant influence on prefrontal activity during executive cognition and anticipation of reward. |
| Conclusions | Our findings, combined with evidence from preclinical and animal studies, suggest that HOMER1 plays a role in the etiology of major depression and that the genetic variation affects depression via the dysregulation of cognitive and motivational processes. |
Relationships reported by
Rietschel, 2010
| 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)) |
|
MDD
|
syndrome |
rs7713917 (rs7713917) |
SNP |
P-value = 1.48E-6 |
rs7713917 showed nominally significant association in both the genome-wide association study and the replication samples(p(combined) = 1.48E-6). Further evidence for HOMER1 was obtained through gene-wide analysis while conditioning on the genotypes of rs7713917 (p(combined) = 4.12E-3). |
Positive
|
|
MDD
|
syndrome |
rs9943849 (rs9943849) |
SNP |
P-value = 3.24E-6 |
rs9943849 showed nominally significant association in both the genome-wide association study and the replication samples (p(combined) = 3.24E-6). |
Positive
|
