It is easier to target a known physiological phenomenon than an emotional state with uncertain biological ties. While conventional treatments for Major Depressive Disorder (MDD) focus on promoting serotonin neurotransmitter levels, much about the mental illness’ origin remains shrouded in obscurity.
However, in August 2016, Nature and Genetics journal published the results of a genome-wide association study, revealing approximately fifteen genomic loci which may contribute to the onset of depression. Investigating the genetic foundations of depression could lead to advanced comprehension of the disorder’s pathogenesis and development of more effective biological remedies .
Collaboration With 23andMe
The branching genetic groundwork of an ailment such as depression operates like an ocean riptide; it ensnares beneath the surface without disturbing the upper waters at large. In other words, it is an insidiously active force which may not be visible upon initial survey of a given population. An earlier statistical study by the Psychiatric Genomic Consortium failed to pinpoint any genetic basis for depression because its mass participant pool of over 17,000 individuals was still insufficient to highlight overarching trends .
Through collaboration with 23andMe, a genotyping service which provides customers with personalized DNA datasets, researchers were able to significantly expand the volume of their study populations. 23andMe conducted elective surveys, gathering self-reported customer input about depression diagnoses and symptoms . 75,607 people testified to a major depression diagnosis. 231,747 people were depression-free, serving as a readily available control population. The scientists on the project were able to analyze 23andMe’s stored genetic data about the contributing individuals’ genomes to identify common threads .
Using 23andMe’s information, the researchers tracked the prevalence of single-nucleotide polymorphsims (SNPs) in Major Depressive Disorder sufferers. An SNP is a common genetic variation where an isolated nucleotide is of a different type than expected; for example, adenine appears instead of cytosine. Many bear no implication on practical bodily function, but changes occurring in key gene regions may be linked to numerous diseases . While a number of SNPs rose to significance in the depression study, two particular ones claimed the frontal spotlight. One hailed from the area of the OLFM4 gene, a region linked to activity in the amygdala and medial temporal lobe. The other prominent SNP locus appeared near the MEF2C and TMEM161B genes; both play roles in brain function. These two focal SNPs were flagged as potential genetic markers for depression .
Further narrowing the frame of concentration, the researchers cross-referenced meta-analyses from 23andMe and the Psychiatric Genomic Consortium. Then, advancing one step further, they juxtaposed these meta-analyses against a third set of data, a replication cohort using an independent batch of functionally equivalent 23andMe participants. By overlapping all three studies’ identified SNPs of interest, the researchers were able to zero in on the likeliest major depressive components. Overall, 15 genomic regions boasting 17 discrete SNPs were implicated by statistical determination .
Once these key SNPs were identified, the researchers performed tissue and gene set enrichment analysis – methods which could determine whether the genome states and expression levels of the catalogued depressive individuals significantly differed from those of non-depressive individuals . The results tested positively; it seemed that the SNPs were specifically enriched in central nervous system genes active in neurodevelopmental transcriptional regulation. This finding further solidified the SNPs’ expected links to clinical depression .
Since genes have the capacity to engage in multiple simultaneous functions, the researchers were curious to see if the genomic loci and SNPs related to depression were involved in any other psychiatric disorders. The SNPs present in Major Depressive Disorder did, in fact, display statistical association with schizophrenia and neuroticism. Clearly, the underlying genetic web of psychiatric phenomena is more intertwined than once expected .
Utilization of self-report data is an entirely novel way to track physiological patterns. Clinical interviews are costly and time-consuming, while 23andMe’s innovative survey system was able to cull large-scale data by casting a broader net. By comparing the genetic data sets of the Psychiatric Genomic Consortium’s clinically determined MDD cases with 23andMe’s self-report style, the researchers were even able to confirm the overall veracity of the self-report approach. The newly uncovered gene regions and SNPs represent newfound hope in the battle against Major Depression, a step toward engineering more targeted treatment options .