Supplementary Material for: Molecular and Genetic Characterization of Depression: Overlap with Other Psychiatric Disorders and Aging
Ding Y.
Chang L.-C.
Wang X.
Guilloux J.-P.
Parrish J.
Oh H.
French B.J.
Lewis D.A.
Tseng G.C.
Sibille E.
10.6084/m9.figshare.4565038.v1
https://karger.figshare.com/articles/dataset/Supplementary_Material_for_Molecular_and_Genetic_Characterization_of_Depression_Overlap_with_Other_Psychiatric_Disorders_and_Aging/4565038
<p>Genome-wide expression and genotyping technologies have uncovered the
genetic bases of complex diseases at unprecedented rates. However,
despite its heavy burden and high prevalence, the molecular
characterization of major depressive disorder (MDD) has lagged behind.
Transcriptome studies report multiple brain disturbances but are limited
by small sample sizes. Genome-wide association studies (GWAS) report
weak results but suggest an overlapping genetic risk with other
neuropsychiatric disorders. We performed a systematic molecular
characterization of altered brain function in MDD using meta-analysis of
differential expression of 8 gene array studies across 3 corticolimbic
brain regions in 101 subjects. The identified ‘metaA-MDD' genes suggest
altered neurotrophic support, brain plasticity and neuronal signaling in
MDD. Notably, metaA-MDD genes display a low connectivity and hubness in
coexpression networks as well as a uniform genomic distribution, which
is consistent with diffuse polygenic mechanisms. We have integrated
these findings with results from over 1,800 published GWAS and show that
genetic variations nearby metaA-MDD genes predict a greater risk for
neuropsychiatric disorders, and notably for age-related phenotypes, but
not for other medical illnesses (including those frequently co-occurring
with depression) or body characteristics. Collectively, the
intersection of unbiased investigations of gene function (transcriptome)
and structure (GWAS) provides novel leads to investigate molecular
mechanisms of MDD and suggests common biological pathways between
depression, other neuropsychiatric diseases and brain aging.</p>
2017-01-19 14:51:18
Depression
Transcriptome
Meta-analysis
Genetic association
Medical illnesses