View Full Version : Study: Genetic overlap_major psychiatric disorders


Dizfriz
08-12-13, 09:31 AM
An article on Science Daily News http://www.sciencedaily.com/releases/2013/08/130811150815.htm?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+sciencedaily%2Fhealth_medicin e%2Fadd_and_adhd+%28ScienceDaily%3A+Health+%26+Med icine+News+--+Attention+Deficit+Disorder%29

An international consortium has shown for the first time evidence of substantial overlap of genetic risk factors shared between bipolar disorder, major depressive disorder and schizophrenia and less overlap between those conditions and autism and attention deficit-hyperactivity disorder (ADHD), according to a study published this week in Nature Genetics' Advance Online publication.

This supports my thinking that many of the psychiatric disorders are connected in a complex genetic neurobiological net. How it is going to shake down I don't know but as I read more on genetics, I am becoming more convinced that this could be of great significance in treating these disorders.

Here is the first paragraph

An international consortium has shown for the first time evidence of substantial overlap of genetic risk factors shared between bipolar disorder, major depressive disorder and schizophrenia and less overlap between those conditions and autism and attention deficit-hyperactivity disorder (ADHD), according to a study published this week in Nature Genetics' Advance Online publication.

Here is the abstract http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.2711.html

I just thought it interesting. It is an exciting time to be alive.

Dizfriz

Amtram
08-12-13, 12:06 PM
The NIH article (http://www.nih.gov/news/health/aug2013/nimh-12.htm) arrived in my inbox today, too. I hadn't yet looked at other news sources, so I don't know if this is a duplication of effort, but this article also shows a graph with several different conditions' known SNPs related to heritability. The surprise at lack of overlap possibly comes from the fact that ADHD currently has the highest number of identified SNPs - so "common sense" would dictate that it must have a lot of overlaps.

The first five on the graph are the ones that The Lancet found common genetic patterns among, so it could be that this work is building upon that and teasing out much more subtle patterns. Very interesting. Thanks for sharing.

peripatetic
08-12-13, 02:00 PM
I find the graph really interesting. I am not especially surprised by there being more of some, less of others. I'm actually more surprised certain ones are as common as depicted in the graph. I do have a question about interpreting the study, or the findings, but perhaps better addressed with a message. Thanks for posting this, Diz!

mildadhd
08-12-13, 11:57 PM
What are genetic overlap, heritabilities and coheritabilities?


The first 3 conditions have lots of overlap.

But the last 2 conditions have less of overlap, with the first three conditions?


Is there a list of the genes involved for each of the 5 conditions?



Peripheral

Addersaurus
08-13-13, 07:33 AM
Like what Peripheral would it be possible to get a list of these overlapping (and non overlapping) genes?

And more importantly any other associated functions of those genes.

Dizfriz
08-13-13, 08:38 AM
Like what Peripheral would it be possible to get a list of these overlapping (and non overlapping) genes?

And more importantly any other associated functions of those genes.
You can read the abstract at the site given. If you want the article itself, it is behind a paywall but may well become available free soon. Sometimes significant articles do.

You may be able to get a copy from a library especially a university based one. Many times they have programs to work with the general populations.

Dizfriz

Addersaurus
08-13-13, 10:48 AM
Do you have access? I can't see the abstract, are you not permitted to post the gene lists from the article here? Would you be able to PM me the list instead?

Amtram
08-13-13, 10:56 AM
The genetic overlap is not necessarily entire genes. It makes this stuff a lot easier to understand if you don't think of "genes" as some kind of standard unit. The studies that look at alleles or Single Nucleotide Polymorphisms are also going to talk about "genes" and use the term "genetic," but the influence of how much material is included in the gene, where it is located in the genome, and whether it's half of a pair inherited from both parents is too important to overlook.

Addersaurus
08-13-13, 12:24 PM
What I was wanted to find out was if there was any meaning or context for these results other than simply there is some genetic overlap (which i do not think is groundbreaking news).

Amtram
08-13-13, 01:48 PM
Well, then, you should read the articles. Follow the research. I don't see anything terribly confusing, just complex.

Dizfriz
08-13-13, 02:12 PM
Do you have access? I can't see the abstract, are you not permitted to post the gene lists from the article here? Would you be able to PM me the list instead?
I don't have access so I cannot send you anything.

I was able to go right to the abstract in the link in the OP. I don't know what could be happening to you with this.

Dizfriz

Abi
08-13-13, 02:18 PM
i could also access the abstract.

Amtram
08-13-13, 02:27 PM
Accessing abstracts is easy. It's full texts that are hard to find. Sometimes if you google the authors or the title of the study, you can find some good reviews or critiques of the work from other scientists, but that depends a lot on how long ago the study was published and how much of an impact it might have.

mildadhd
08-13-13, 11:19 PM
I read the links, but I could not tell if there was a substantial lapover between ADD and three most common comorbidities, anxietties, depressions and addictions?




Peripheral

mildadhd
08-18-13, 09:14 PM
The NIH article (http://www.nih.gov/news/health/aug2013/nimh-12.htm) arrived in my inbox today, too. I hadn't yet looked at other news sources, so I don't know if this is a duplication of effort, but this article also shows a graph with several different conditions' known SNPs related to heritability. The surprise at lack of overlap possibly comes from the fact that ADHD currently has the highest number of identified SNPs - so "common sense" would dictate that it must have a lot of overlaps.

The first five on the graph are the ones that The Lancet found common genetic patterns among, so it could be that this work is building upon that and teasing out much more subtle patterns. Very interesting. Thanks for sharing.



"Yet this still leaves much of the likely inherited genetic contribution to the disorders unexplained — not to mention non-inherited genetic factors. For example, common genetic variation accounted for.."

28 % of ADD,

"but evidence from twin and family studies estimate its total heritability at.."

75% of ADD?

47 % of supposedly "inherited genetic contribution", unexplained.

(In addition to the previous 25 % non inherited genetic contribution determined by twin and family studies?)



The study results also attach numbers to molecular evidence documenting the importance of heritability traceable to common genetic variation in causing these five major mental illnesses. Yet this still leaves much of the likely inherited genetic contribution to the disorders unexplained — not to mention non-inherited genetic factors. For example, common genetic variation accounted for 23 percent of schizophrenia, but evidence from twin and family studies estimate its total heritability at 81 percent. Similarly, the gaps are 25 percent vs. 75 percent for bipolar disorder, 28 percent vs. 75 percent for ADHD, 14 percent vs. 80 percent for autism, and 21 percent vs. 37 percent for depression.

http://www.nih.gov/news/health/aug2013/nimh-12.htm

Dizfriz
08-18-13, 10:03 PM
From Peripheral "Yet this still leaves much of the likely inherited genetic contribution to the disorders unexplained not to mention non-inherited genetic factors. For example, common genetic variation accounted for.."

28 % of ADD,

"but evidence from twin and family studies estimate its total heritability at.."

75% of ADD?

At least a "gap" of 47 % unexplained. From the article: The study results also attach numbers to molecular evidence documenting the importance of heritability traceable to common genetic variation in causing these five major mental illnesses. Yet this still leaves much of the likely inherited genetic contribution to the disorders unexplained not to mention non-inherited genetic factors. For example, common genetic variation accounted for 23 percent of schizophrenia, but evidence from twin and family studies estimate its total heritability at 81 percent. Similarly, the gaps are 25 percent vs. 75 percent for bipolar disorder, 28 percent vs. 75 percent for ADHD, 14 percent vs. 80 percent for autism, and 21 percent vs. 37 percent for depression.http://www.nih.gov/news/health/aug2013/nimh-12.htm

While I cannot tell without reading the report, what I understand they are saying is that they have been able to isolate some possible SNPs (single-nucleotide polymorphism-specific gene variations) that may connect to these disorders.

Here they are discussing the difference between what they have found and what is expected.

For ADHD, the twin and family studies indicate about a 75 percent heritability factor but the SNPs they found may only account for 28 percent of the total. That means they have isolated some of the gene locations but not nearly all.

A key sentence is "Yet this still leaves much of the likely inherited genetic contribution to the disorders unexplained."

So you can see the "gap" is simply between what they have found in the study and what they might expect to find in the future. They do not seem to be questioning the heritability rates rather they are trying to correlate them to specific locations on the genome and have only addressed a part of the total. That is what they mean by "unexplained" No mystery here.

Interesting point,

Dizfriz

mildadhd
08-18-13, 10:19 PM
72 % unexplained by molecular evidence, common genetic variation accounted for 28%, according to the information posted.

Peripheral

Amtram
08-18-13, 10:26 PM
My own unprofessional opinion is that we're finally learning that genes do not determine conditions, but symptoms. A gene tells a Hox6 protein what individual, very specific, cells to build. Depending on when during development that happens, or doesn't, a particular part of the brain will or won't be built.

The brain is the most complex structure in all of biology, and the human brain the most complex among those. A moment's interruption (or lack of interruption) in development can cause a significant difference in outcome.

I have experienced, first hand, the effect of physical factors in brain function. To me, there is no question that something that affects the physical function or development of the brain will result in disorders and/or dysfunction.

mildadhd
08-18-13, 10:45 PM
These included variation in two genes that code for the cellular machinery for regulating the flow of calcium into neurons. Variation in one of these, called CACNA1C, which had previously been implicated in susceptibility to bipolar disorder, schizophrenia and major depression, is known to impact brain circuitry involved in emotion, thinking, attention and memory functions disrupted in mental illnesses.

http://www.nimh.nih.gov/news/science-news/2013/five-major-mental-disorders-share-genetic-roots.shtml

mildadhd
08-18-13, 10:54 PM
Another important area of focus will be epigenomics--the mechanisms through which environmental and experiential influences interact with genes to control their function. Epigenetic changes describe alterations to DNA structure and packaging that do not affect the underlying sequence. For example, a rare CNV associated with ASD deletes the gene that codes for the oxytocin receptor. In many individuals with ASD who do not have this deletion, the gene is silenced by epigenomic modifications, essentially producing the same outcome as a gene deletion.6

Director’s Blog: In Search of the Missing Genetic Signals (http://www.nimh.nih.gov/about/director/2010/in-search-of-the-missing-genetic-signals.shtml)

Addersaurus
08-19-13, 05:06 AM
As far as I understand, I don't think it has ever been in doubt that physical brain damage will have some effect on the brain.

However, as for "delayed development", it means little unless you understand why there would be delayed development.

Also what is to say delayed development is not preferable in some regards? I see no reason why an area of delayed development should necessarily result in disorder as long as it does develop. (an example I used before was human babies take longer to develop than the 40 days mosquitoes take to reach sexual maturity.)

Where the brain is concerned my understanding is it is generally a case of use it or lose it. If a brain has certain experiences, especially early in development it reacts.

Disorders would therefore first and foremost be resultant of environmental reactions/expectations (timing dependant) occurring before becoming a truly interactive component themselves (and the resultant "comorbids" etc).

The brains state, whether classified as "disordered" or not, is always subjectively rational.

Dizfriz
08-19-13, 09:01 AM
Peripheral,

Two very good finds especially the NIMH Directors Blog one. Thanks!


Director’s Blog: In Search of the Missing Genetic Signals (http://www.nimh.nih.gov/about/director/2010/in-search-of-the-missing-genetic-signals.shtml)

http://www.nimh.nih.gov/news/science...ic-roots.shtml (http://www.nimh.nih.gov/news/science-news/2013/five-major-mental-disorders-share-genetic-roots.shtml)


Two from from the Director's Blog I especially liked:

As we look closer, it’s clear that there are many different forms of variation in the genome and many potential genomic roads to mental disorder.And the last sentence:
Clearly, genomics is only part of the cause for serious mental illness, but it is a part that is finite and tractable and, in the near future, offers our best portal to the pathophysiology of these complex disorders.Thanks again for finding and sharing them.


Dizfriz

Amtram
08-19-13, 09:47 AM
And it also makes sense to work from general to complex when looking at any human condition. The most basic aspect of the brain, like everything else in the body, is its physical structure. The functions of individual structures tend to remain stable, and many of the connective pathways among those structures are common to the normal human brain and are established before birth. So you check the things that are standard/stable/common among normal brains first and compare. If something that's supposed to be a certain way is different, that's going to point you in the direction of the next thing to look at.

mildadhd
08-19-13, 10:28 PM
Thank You, Dizfriz!

Another important area of focus will be epigenomics--the mechanisms through which environmental and experiential influences interact with genes to control their function. Epigenetic changes describe alterations to DNA structure and packaging that do not affect the underlying sequence. For example, a rare CNV associated with ASD deletes the gene that codes for the oxytocin receptor. In many individuals with ASD who do not have this deletion, the gene is silenced by epigenomic modifications, essentially producing the same outcome as a gene deletion.6

Director’s Blog: In Search of the Missing Genetic Signals

Peripheral