Abstract
Previous studies aiming to identify the transcriptome signature of depression show inconsistent results with low replicability at the single gene level in both brain and peripheral tissues. The complexity of the depression phenotype may contribute to this inconsistency. An advance in this field could be made by utilising systems biology approach. In this study, we analysed whole blood transcriptomes of 521 elderly people from the general population (The Sydney Memory and Aging Study, MAS) to identify molecular networks involved in geriatric depression. Depression was assessed according to DSM-IV criteria yielding both categorical and continuous depression phenotypes.Pre-processing of 47,323 probes (Illumina HT-12 v4) resulted in the 11,018 top-varying genes for downstream analyses. Pre-processing included maximum likelihood estimation (MLE) background correction, variance-stabilising (VST) transformation, quantile normalisation and filtering by detection p-value (p<0.01 in ≥50% of samples) and coefficient of variation (0.01).Using WGCNA package (R) we constructed the co-expression network consisting of 29 modules, two of which were associated with depressive symptoms. Both modules showed a highly significant correlation between module membership (MM) and gene significance (GS) measures (r=0.55, p=1e-07, r=0.4, p=0.0011), indicating that genes in these modules are highly significantly associated with depression. Further analysis showed that 37 and 17 genes respectively from the two “depression modules” are significantly associated with depressive symptoms (p<0.05), the top in each module being two protein-coding genes involved in metabolic process regulation by reactive oxygen species PCYOX1L, prenylcysteine oxidase-like (p<0.001) and PRCP, prolylcarboxypeptidase (p<0.05). Our results are in line with the oxidative stress hypothesis of depression. In addition, using IPA software we will present the results from pathway analyses performed on genes identified as relevant to depression in this study. A replication study (Older Australian Twins Study, OATS) is currently underway in a sample of 324 subject of similar age, gender and ethnicity.
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