For a long time, the study of depression has been from a
psychological perspective. Studies investigating the genetic aspects of mental
illness have often rendered fruitless outcomes, over-ambitious results and
rifts between communities of geneticists. However, recently published in Nature,
a study including several datasets of human genomes support the strongest argument
yet for a genetic association to Major Depressive Disorder.
Depression is a type of mental illness that can develop in
any individual regardless of age, gender or lifestyle. Its exact workings
remain a mystery, as each case of depression varies from individual to
individual – just like cancer. General belief is that an imbalance of chemicals
in the brain, including neurotransmitters, causes depression. As a result, “wrong”
genes become expressed (or inhibited) inside cells and different areas of the
brain end up functioning less or abnormally.
Research released in collaboration with genome-sequencing
company 23andMe earlier this year has posed genetic links to MDD in adult
Europeans. The business sells gene-test kits for less than £200, and are easy
to obtain through it’s online store.
Until recently most data produced by the organisation was
made for customers as a personal, entertaining insight into their ethnic
heritages. As well as investigating their genetic miscellanies, users of the
service can accept to release their genome for research within a multitude of
studies.
The paper,
lead by geneticist Dr. Ashley R. Winslow, is the largest study of it’s kind.
The research uses a technique called Genome-wide Association Study. This is a commonly-used
bioinformatical approach that takes the DNA of people suffering from a disease
and compares it, base-by base, to healthy DNA genomes. In this case, the
healthy genomes and the genomes of
individuals with MDD both came from consenting-users of 23andMe.
Individuals
gave important “self-report data” to the organisation, alongside their DNA
submissions. Dr. Winslow’s team performed a meta-analysis, combining the
23andMe data with previous MDD association-study datasets. Using the
self-reports the researchers confirmed a total of 75,607 individuals declaring
some history of clinical depression. This group was transferred to a new
dataset and compared to the 231,747 individuals that reported no personal history
of depression.
After the
comparative assessment, 5 stand-alone “variants” from 4 regions were identified
as being unique between the two groups. Upon analysis of loci (their locations
in the genome) the team uncovered 17 independent Single Nucleotide
Polymorphisms/ mutations from 15 regions that seemed to have a large effect on
the genome.
Note: the 17 SNPs were identified after loci with P
values more than 1 x 10-5 were excluded.
In previous studies using whole genome sequences some of
these loci had shown associations with psychiatric traits. This means that the
regions aforementioned can be scrutinised in individuals to observe whether
certain SNPs in these areas can increase the risk of MDD.
The paper aims to set a “diving-board” for more investigations into the
biology of depression. As a large undertaking by Winslow et al., this novel
study in the field has demonstrated the potential of larger collaborative datasets
that are made publicly available. The results could also encourage
second-glances at previous studies, such as Cai, Bigdeli, Kretzschmar & Li
(2015), which pointed links between MDD and 2 loci in female Chinese
populations.
Considering the future implications of public, crowdsourced genetic
datasets it would not be unfair to suggest that we could begin to investigate
the mechanics of these identified loci. New drugs could be synthesised that target
the variants within these regions, and advanced methods of MDD detection could
be a possibility. However, the latter may be a long way off. From what is known
about its genetic association the risk of depression is down to mutations at
hundreds of loci, each having a miniscule effect on the overall outcome.
What can definitely be said is that these findings are a positive re-enforcement,
if not an affirmation, that mental illness does
has a genetic factor. We now know even-more-so that lifestyle may not be a
preventive or causative issue for the development of psychological disorders in
some individuals.
References:
·
Winslow, A. R., Hyde, C. L., Nagle, M. W.,
Tian, C., Chen X., Paciga S. A., Wendland J. R., Tung J. Y., Hinds D. A.,
Perlis R. H. (2016) Identification
of 15 genetic loci associated with risk of major depression in individuals of
European descent, Nature. DOI: 10.1038/NG.3613
·
日本語要約 (2015) Sparse whole-genome sequencing
identifies two loci for major depressive disorder, Nature, 588-591. DOI:
10.1038/nature14659
·
“Study
points way to finding genes affecting depression risk” – Malcom Ritter
(09/2016)http://hosted.ap.org/dynamic/stories/U/US_MED_DEPRESSION_GENETICS?SITE=PASUN&SECTION=HOME&TEMPLATE=DEFAULT
·
“23andMe
Pulls Off Massive Crowdsourced Depression Study” – Antonio Regalado (09/2016) https://www.technologyreview.com/s/602052/23andme-pulls-off-massive-crowdsourced-depression-study/
·
Harvard Health Publications http://www.health.harvard.edu/mind-and-mood/what-causes-depression
- Image 1: http://www.wwu.edu/healthyliving/education/Depression/images/causesDNA.png
- Image 2: https://upload.wikimedia.org/wikipedia/commons/thumb/e/ec/23andMe_logo.svg/2000px-23andMe_logo.svg.png
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