View Full Version : Development in the womb...and epigenetics


LynneC
05-02-14, 02:26 PM
I found this at Science Daily, and the full version of the study is also available. The study seems rather technical but I am going to give it my best shot when I have some time to spend on it.

Development in the Womb; New Insight on Epigenetic Influence on Baby
http://www.sciencedaily.com/releases/2014/04/140428074640.htm
'The results showed that genetic differences alone best explained 25 per cent of the epigenetic variation between babies, with the remaining 75 per cent best explained by the interaction of genetic differences and the prenatal environment.'
This was in Science Daily, so I can't say that the study supports that conclusion...we all know how the media sometimes misinterpret scientific studies. :p

And the link to the full study:
http://genome.cshlp.org/content/early/2014/04/07/gr.171439.113.full.pdf+html

Abi
05-02-14, 02:47 PM
The results showed that genetic differences alone best explained 25 per cent of the epigenetic variation between babies

Am I drunk, or is this gibberish?

Diz?

Amtram?

LynneC
05-02-14, 03:17 PM
Am I drunk, or is this gibberish?

Diz?

Amtram?
Not directed to me, but since I am the OP, I'll put my 2 cents in... :p

As I mentioned above, this is the conclusion presented in Science Daily, not necessarily the conclusion in the study. Another thing to note is that there is no way that any inferences can be drawn from this study regarding epigenetics in the womb and ADHD.

That being said, I think as the science of DNA (including our understanding of epigenetics) becomes more advanced, our understanding of the influences affecting any manner of medical conditions, including those that fall into the mental health category, will evolve.

Abi
05-02-14, 03:30 PM
It's not so much that I disagree with the quoted sentence, it's that I don't understand what it means.

namazu
05-02-14, 03:50 PM
This bit of the intro might help explain what they're trying to tease out:

The relationship between inter-individual variation in the epigenome, especially DNA methylation, and
disease risk is an area of intense research interest. While the effect of fixed genetic variation on DNA
methylation is apparent in studies of allele-specific methylation and genomic imprinting, there is also
emerging evidence for environmental influences as a source of epigenomic variation. Perinatal cohort
studies offer a unique opportunity to explore the origins of variation across the epigenome, and in
particular the extent to which fixed genetic variation can moderate the relationship between prenatal
environmental factors and epigenetic status at birth.

[...]

In this paper we focus on examination of the relative influences of genotypic, environmental and gene x
environment interactive effects on the neonatal methylome. Recent studies describe evidence for gene
x environment interactions (GxE effects) on DNA methylation. (Yousefi et al. 2013) found that LEPR
genotype interacted with maternal smoking to associate with methylation of LEPR. A SNP within the
IL4R gene combined with methylation at a CpG site within the same gene predicts risk of childhood
asthma (Soto-Ramirez et al. 2013). Moreover, (Klengel et al. 2013) found that interaction of FKBP5
genotype and early childhood trauma affects methylation of FKBP5 intron 7, FKBP5 expression and
subsequent deregulation of glucocorticoid receptor signalling. The proportions of inter-individual
variation in methylomes that are driven by genotype, environment or an interaction of gene and
environment (GxE) are currently unknown. To clarify the relative influence of gene and in utero
environment on epigenetic status at birth we studied variation in genome-wide DNA methylation
patterns in umbilical cord samples from 237 Asian neonates using the InfiniumHumanMethylation450
BeadChip together with genotyping and extensive measures of in utero environmental conditions. We
report that genotype, and in particular GxE interactions, explain substantial proportions of interindividual
variation in the methylome at birth.

Basically, some epigenetic variation is a consequence of instructions encoded in DNA. Some results from environmental factors. Here, the authors were attempting to tease out how much of the variability in methylation in the DNA in neonates could be attributed to / explained by genotypic differences.

Later in the paper, the authors state that
Methylation levels at ~25% of the 1423 VMR-CpGs were best explained by genotype
alone, whilst the rest were best explained by GxE models (Figure 5A).
Purely genotypic models best matched the patterns of methylation seen at 25% of the stretches of DNA they looked at (VMR = variably-methylated regions), and interactions between genes and environment best explained the remainder. The authors state that environment-only models were never the best-fitting models for the variability seen in these regions.

LynneC
05-02-14, 03:55 PM
After perusing the study, I don't see the 25% statistic. I didn't read the entire study, but it seems that the authors conclude that genotype and genotype/ environmental interactions explain most of the epigenetic changes. I believe what the authors are saying is that GENOTYPE influences the effect that environment will have on epigenetics. This makes sense to me...

ETA...posted before reading Namazu's reply...

namazu
05-02-14, 04:14 PM
After perusing the study, I don't see the 25% statistic. I didn't read the entire study, but it seems that the authors conclude that genotype and genotype/ environmental interactions explain most of the epigenetic changes. I believe what the authors are saying is that GENOTYPE influences the effect that environment will have on epigenetics. This makes sense to me...

See my post above for the statistic...it's in the section called "GxE models best explained variation in methylation at most VMR-CpGs" on p.8.

You're right that the authors are saying that environment alone does not appear to be the best explanation for variability in methylation at the population level in any of the epi/genomic regions they studied. Genotype-alone models best fit a minority of the regions, while gene-environment interactions appeared the best fit for 75% of the epigenomic regions studied.

Note also that the authors give many caveats, advising readers not to take these numbers as Gospel -- see the 2nd paragraph, p.11 for discussion of some of the limitations of their models (which apparently didn't fit particularly well).

But their overall conclusion, Nevertheless our data serve to underscore the importance of GxE interactions and
suggest that models of epigenetic variation should consider such interactive influences.
seems well-supported!

Interestingly, they note that underestimating the role of genotype may actually lead to underestimates of the role of environment, when a particular genotype leaves a subgroup of the population very vulnerable to specific environmental influences.

Abi
05-02-14, 04:14 PM
SO we have an example of "Science Writers" (BA Journalism dropouts with a few freshman science courses) reading a study, totally misunderstanding it, and writing an article about it?

ETA - also written before Namazu's response

namazu
05-02-14, 04:19 PM
SO we have an example of "Science Writers" (BA Journalism dropouts with a few freshman science courses) reading a study, totally misunderstanding it, and writing an article about it?

ETA - also written before Namazu's response
I don't think the Science Daily article was terrible, but they did throw out the 25%/75% statistic without the nuance or context needed to understand it.

TygerSan
05-02-14, 04:23 PM
Science Daily tends to be pretty good. The truth of the matter is most science journalists *aren't* scientists, and therefore the nuances get lost. (Well, that and they are writing for people who don't get nuance).

Dizfriz
05-02-14, 04:31 PM
Good article. It is going to be interesting in how this replicates.

A few notes if interest


The environmental measures selected for analysis included proxy factors such as birth weight and gestational age, maternal smoking and depression, all of which are known to influence a broad range of developmental outcomes. They were looking at a limited number of factors as they must.

we failed to find VMR-CpGs that were best explained by environmental conditions independent of genotype. This finding emerged despite the considerable evidence for the effects of environmental factors in pregnancy on both epigenetic states. The way I read this is that without the genetic background is present, the epigenetic effects will not be. That is pretty much as I see it from my inexpert view.

This observation is consistent with the emerging view that genotype can determine the degree of environmentally-induced phenotypic plasticity (i.e. so called ‘plasticity genes’ (Belsky et al. 2009; Simons et al . 2011) and that epigenetic mechanisms serve to maintain environmentally-induced phenotypic variation Makes sense to me at least some. We shall have to wait and see how it turns out.

Now to the important part. Conclusions Our report, to our knowledge, is the first attempt to quantify the relative influence of genotype and environment, and their interaction on the human epigenome. This quantification is important as many reports compare DNA methylation to phenotype independent of genotype . Our results strongly suggest that genotype is an essential factor in these relationships. In particular, it is an important question to address in neonates because the influence of pre-natal environment on future disease risk is intensely studied with respect to subsequent risk of illness. Our findings suggest that such studies should include an assessment of the degree to which environmental influences are moderated by genotype. This seems to support my understanding of the script as the genotype and the director/actors as the epigenetic factors. That is unless I misread it.

Looks like some good areas for future research. Epigenetics is a very hot subject right now.

Lynne, good find, thanks for posting it.

Dizfriz

LynneC
05-02-14, 07:01 PM
I think that this type of research is what the future looks like...

Genes and environment are inextricably entwined...the key is to figure out what we can do individually to influence our genetic makeup...
(and my opinion is, there is much we can do :) )

Amtram
05-02-14, 07:36 PM
I was forwarded this link by CW at Emerging Epigenetics: http://www.nature.com/ncomms/2014/140429/ncomms4746/full/ncomms4746.html This deals with diet at the time of conception, as a mechanism to establish initial methylation patterns. Consistently, the findings in epigenetic research show that if there is going to be an epigenetic change that produces an observable result, it needs to happen early in life, especially before cell differentiation.

However, one thing that was also told to me by several epigeneticists is that the evidence that dietary change of any kind can unmethylate is nonexistent so far, and that there has been no evidence from any studies in humans at all that diet produces epigenetic changes in adults.

Dizfriz
05-02-14, 08:30 PM
However, one thing that was also told to me by several epigeneticists is that the evidence that dietary change of any kind can unmethylate is nonexistent so far, and that there has been no evidence from any studies in humans at all that diet produces epigenetic changes in adults.

I guess that it keeps needing to be emphasized, epigenetics is not a magic wand that accomplish anything that can be imagined. It just doesn't work that way.

Right now, as far as I know, there is nothing linking diet into epigenetics in adults.

That does not mean that it is not possible but there is a huge difference between "possible" and "is"


Dizfriz

Amtram
05-03-14, 01:34 PM
http://scienceblogs.com/insolence/2013/02/11/epigenetics-you-keep-using-that-word-i-do-not-think-it-means-what-you-think-it-means/

Dizfriz
05-03-14, 02:53 PM
I thought this thread was supposed to be about epigenetics? http://scienceblogs.com/insolence/2013/02/11/epigenetics-you-keep-using-that-word-i-do-not-think-it-means-what-you-think-it-means/
Good article. Its a keeper.

Dizfriz

LynneC
05-04-14, 08:45 AM
I guess that it keeps needing to be emphasized, epigenetics is not a magic wand that accomplish anything that can be imagined. It just doesn't work that way.

Right now, as far as I know, there is nothing linking diet into epigenetics in adults.

That does not mean that it is not possible but there is a huge difference between "possible" and "is"


Dizfriz
This is an area that I am keenly interested in; I do think that it may be possible to effect some changes epigenetically through diet and/or supplementation. B vitamins in particular are an avenue that bears delving into because they play a crucial role in methylation cycles.
(Again, I am not referring to ADHD specifically here)

Dizfriz
05-04-14, 10:29 AM
This is an area that I am keenly interested in; I do think that it may be possible to effect some changes epigenetically through diet and/or supplementation. B vitamins in particular are an avenue that bears delving into because they play a crucial role in methylation cycles.
(Again, I am not referring to ADHD specifically here)
It would be nice if this could happen. Who knows, this is so new that is no telling how it is going to play out in the next decade or so.

Dizfriz

mildadhd
05-06-14, 02:27 PM
I am curious to know how exposure to prenatal toxins fits into this discussion?

P

Amtram
05-06-14, 02:46 PM
1. Define "toxins."

JJJJJJJJJJ
09-25-14, 12:01 AM
This is an area that I am keenly interested in; I do think that it may be possible to effect some changes epigenetically through diet and/or supplementation. B vitamins in particular are an avenue that bears delving into because they play a crucial role in methylation cycles.
(Again, I am not referring to ADHD specifically here)

LynneC I think you are tying this into ADHD quite well. This touches on the reason I recently joined the group, discussion of natual amphetamine-like trace amines.

The natural trace amine, N-Methylphenethylamine, is similar to amphetamine. (Adderall is essentially amphetamines.). N-Methylphenethylamine is downstream from Phenylalanine, the amino acid that feeds into the brain's catecholamines (Cats). Low levels of Cats are associated with ADD. A diagram of the Cats & trace amines can be seen here. (http://en.wikipedia.org/wiki/N-Methylphenethylamine)

You'll notice "Methyl" in N-Methylphenethylamine. It gets its methyl group from the body's primary methyl donor--SAMe. (cf PNMT enzyme (http://en.wikipedia.org/wiki/Phenylethanolamine_N-methyltransferase) ) You can see SAMe in this diagram (http://mercuryandmore.weebly.com/uploads/1/7/6/6/176627/2028914.jpg?480x586) of the methylation cycle and transsulfuration.

A discussion of genes and methylation will certainly include the MTHFR gene involved in production of "methyl folate". This image (http://en.wikipedia.org/wiki/File:MTHFR_metabolism.svg) shows the location where MTHFR is involved in the folate cycle near the methylation cycle.

Additional detail on the transfer of the methyl group from methyl folate to B12 (cobalamin) to homocysteine can be seen in this diagram (http://en.wikipedia.org/wiki/Methylenetetrahydrofolate_reductase) of the intersection of the folate and methylation cycles.

The enzyme involved at the intersections of the folate and methylation cycles, methionine synthase--represented as "MS" in the diagrams above--is known to be quite vulnerable to heavy metals (HMs).

I don't have the link but some studies have indicated an increase in glutathione (GSH, the body's big-gun antioxidant and detox chemical seen in the transsulfuration diagram above) when methylation support was provided. GSH helps the body to get rid of HMs; however, with HMs present, the body has trouble making GSH as described around half-way down this page (http://www.printfriendly.com/print/?source=site&url=http%3A%2F%2Fwww.enzymestuff.com%2Fmethylation .htm)!

If you are not making normal amounts of SAMe (cf methylation cycle diagram) then you are not likely to make normal amounts of the amphetamine-like trace amines as well as normal amounts of adrenaline (epinephrine). More on the effect of trace amines and amphetamine on dopamine levels here, (http://en.wikipedia.org/wiki/Phenethylamine) including a nice diagram of a "dopamine neuron."

A friend seemed to fit this description quite well. He had a history of inattentive ADD, Cat depression, sadness/hopeless depression, sleep problems and anxiety. He really struggled to get things done unless he was really interested in them. He had a long history of exposure to lead in his family's renovation construction business and lead was high on his hair test. His urine amino acids reported low levels of dopamine, almost normal levels of noradrenaline (norepinephrine) and very low adrenaline (epinephrine). ( methylation / PNMT enzyme is involved in that conversion ) He had one, not two, of the less desirable variations of MTHFR. When he would take more than the tiniest amount of tyrosine (amino acid that feeds into production of Cats as seen in diagrams above) he would initially feel somewhat better, then he would get a panic attack (high noradrenaline/epinephrine due to poor methylation?).

He responded surprisingly well to Adderall. It allowed him to be productive and so he could work his way out of his financial problems. He was able to go off of the anxiety meds he had been on! Apparently that was largely psychological since he was on the verge of loosing his business, house, etc. Family relationships improved, etc!

I'm sure I'm only touching on one of many potential interactions between genetic and environmental factors that could be tied to ADD. Some people get tested for the COMT gene--cf Cat & amine diagram. Oxidative stress from HMs could be expected to have a negative effect on iron absorption as described here. (http://www.wellnessresources.com/main/printable/stunning_discoveries_regarding_iron_obesity_candid a_thyroid/) Iron is required for the conversion of tyrosine to L Dopa--cf AAAH enzyme in Cat & amine diagram.

There are frequent discussions on HMs vs MTHFR and other genes in the Yahoo HM groups such as Adult Metal Chelation and Frequent Dose Chelation. It is also discussed in autism/aspergers circles, for example, by Autism specialist Amy Yasko, PhD Chemistry.
( Note: 74% of parents of kids with Autism or Aspergers reported benefit from HM detox in this large survey by the Autism Research Institute (http://www.autism.com/index.php/treatment_ratings_asd), the best rating of all of the listed interventions.)

The PhoenixRising group focuses on methylation discussions, including genetic testing. The most dramatic example of a person with a HM problem who responded to methylation support is BradMcB(Stridor). I've followed his case--and brother's case--over the past four years and found them to be compelling. He is also active at PhoenixRising. His dramatic improvements along with rare combinations of genetic variations are described here. (http://www.printfriendly.com/print?url=http%3A%2F%2Fhowirecovered.com%2Fmeet-brad-who-recovered-from-bipolar-disorder%2F) He also had more than a few ADD & Cat depression symptoms.

This is an unrelated example that a supplement can affect epigenetics.

"...“Recently, natural compounds, such as curcumin, epigallocatechin gallate (EGCG), and resveratrol, have been shown to alter epigenetic mechanisms, which may lead to increased sensitivity of cancer cells to conventional agents and thus inhibition of tumor growth.." Summarized by B Richards here (http://www.wellnessresources.com/main/printable/curcumin_helps_change_gene_function_to_combat_canc er/)

Btw EGCG from green tea is touted as useful for ADD as well however I've had enough of digging though my notes for one evening!

SB_UK
09-25-14, 10:50 AM
Heavy metals are found naturally in the earth, and become concentrated as a result of human caused activities. Common sources are from mining and industrial wastes; vehicle emissions; lead-acid batteries (http://en.wikipedia.org/wiki/Lead-acid_batteries); fertilisers, paints and treated woods.

Solar power, electrically powered vehicles, animal-based fertilizer, elimination of paints, wood protection by burning the surface layer can eliminate these HM generating human practices.

Prevention.