DNA methylation

A study of DNA methylation and age

gettingwell4 5+ stars Premium, Epigenetics , ,

This 2014 Finnish human study compared and contrasted the DNA methylation levels of young adults with people age 90:

“We identified 8540 high-confidence CpG [cytosine and guanine separated by only one phosphate link] sites that show a large difference in methylation levels between nonagenarians and young controls and that present high statistical significance in a regression model adjusted for the leukocyte proportion.

The majority of frequently reported CpG sites are hypermethylated with increasing age.

Ageing-associated hypermethylation is concentrated in genes associated with developmental processes as well as DNA-binding and transcription of genes, whereas hypomethylation is not enriched among a specific set of genes.

The largest percentage of the variation in our methylation data was associated with the proportions of different leukocyte subtypes.

We found that only a minority of ageing-associated CpG sites showed an association between methylation and expression levels. Furthermore, only a minority of these genes have been identified as differentially expressed between nonagenarians and young individuals.”

The finding concerning:

“Ageing-associated hypermethylation is concentrated in genes associated with developmental processes as well as DNA-binding and transcription of genes”

was in concert with a referenced 2013 review Aging is not programmed that stated:

“Aging is not and cannot be programmed. Instead, aging is a continuation of developmental growth, driven by genetic pathways.

Aging is a shadow. Its shape is determined by the developmental growth.

Genetic programs determine developmental growth and the onset of reproduction. When these programs are completed, they are not switched off.

Aging has no purpose (neither for individuals nor for group), no intention. Nature does not select for quasi-programs. It selects for robust developmental growth.

Whereas the growth of the body is programmed, the emergence of the shadow is not. Natural selection cannot eliminate the shadow without hurting the “body”.”

The researchers made several points relating the current study and other epigenetic studies.

Regarding DNA methylation and gene expression:

“Due to the methods applied in the present study, not all the effects of DNA methylation on gene expression could be detected; this limitation is also true for previously reported results.

The textbook case of DNA methylation regulating gene expression (the methylation of a promoter and silencing of a gene) remains undetected in many cases because in an array analysis, an unexpressed gene shows no signal that can be distinguished from background and is therefore typically omitted from the analysis.”

Regarding biological age and chronological age:

“It remains to be investigated whether these [CpG] sites are only associated with chronological age or if there are also associations with phenotypic changes related to (successful) ageing.

If these frequently reported sites are only markers of chronological age, markers of biological age are yet to be identified.”

Regarding the rapid progression of technology used in epigenetic studies, they noted several times how what they used was significantly improved over pre-2014 technologies with statements such as:

“Global hypomethylation has been associated with an increasing risk of frailty, but very few other associations between phenotype and DNA methylation have been reported. However, this may be due to technical concerns, as the study by Bell et al. was performed with the 27K array, which almost exclusively contains promoter-associated probes that are not methylated at baseline and can therefore primarily acquire hypermethylation. Phenotype association studies performed with the 450K array or using sequencing techniques are necessary to clarify if hypomethylation is associated with typical ageing-associated phenotypes.”

Compare that with the limitations of the same 450K array acknowledged in A human study of changes in gene expression 2015 study:

“This array queries only 1.6% of all CpGs in the genome and the CpG selection is biased towards CpG islands. Other techniques – whole-genome bisulfite sequencing and methylC-capture (MCC) sequencing, for example – have definite technical advantages (higher resolution and no CpG island selection bias).”

http://www.biomedcentral.com/1471-2164/16/179 “Ageing-associated changes in the human DNA methylome: genomic locations and effects on gene expression”

Is the purpose of research to define opportunities for interventions?

gettingwell4 < 0 Detracted from science, Brain development, Epigenetics, Primal Therapy, Stress , , , , , , , , ,

In this 2014 review, a social scientist first presented an interpretive history of what he found to be important in the emergence of epigenetics. He proceeded into his ideas of “a possible agenda of the social studies of the life-sciences” in the “postgenomic age” with headings such as “Postgenomic biopolitics: “upgrade yourself” or born damaged for ever?”

This perspective included:

“The upgradable epigenome may become the basis for a new motivation to intervene, control and improve it through pharmacological agents or social interventions.

An important trend is the use of epigenetic and developmental findings in the so-called early-intervention programmes.

It is possible that epigenetic findings will become increasingly relevant in social policy strategies.”

In this blog I often highlight research that may help us understand details of how each of us is a unique individual. It’s my view that insofar as research helps each of us understand our unique, real self, we may be able to empathetically understand others’ unique qualities.

Click individual differences for a sample of how researchers explain away uniqueness in order to converge on a study’s desired objectives. There’s seldom an attempt to further understand what caused each subject to develop their unique qualities.

Why would this reviewer advocate that

  • Researchers,
  • People working in the social sciences,
  • People employed or involved in social services, and
  • Their sponsors and employers

intentionally disregard another individual’s unique qualities?

I’ll answer this question from a perspective that explains how this common, reflexive action derives from a person being unable to face the facts of their own life. Pertinent fundamentals of Dr Arthur Janov’s Primal Therapy are:

  1. Pain motivates a person’s unconscious act-outs of their underlying problems.
  2. The behavior that caused a problem is sometimes also the act-out behavior.
  3. Act-outs enable a person to re-experience the feelings of their historical struggles, in a vain attempt to resolve them.
  4. Due to pain barriers, people seldom become consciously aware of and – more importantly – address the causes for their own problematic behavior.
  5. “The patient has the power to heal himself.”

A consequent hypothesis is that a person will often glorify their unconscious act-outs and surround themself with justifications for these actions. For example, a person who can’t sit still may refer to their incessant activity with socially acceptable phrases such as “I’m always busy” or “I love to travel.” They’ll structure their life to enable their unconscious behavior, never questioning how they were attracted to an always-on-the-go occupation such as flight attendant, only vaguely feeling that they were made for it.

The behavior relevant to the current review may be exhibited by a person with a history of having no control over their own life. Following the above first two fundamentals, the pain of historically not having control over their life may motivate them to control other people’s lives.

Unfortunately for everyone who’s affected, such unconscious act-outs don’t resolve anything:

  1. The initiator may achieve some symbolic satisfaction by controlling others’ lives.
  2. This temporary satisfaction doesn’t make the initiator’s underlying problems less painful.
  3. The motivation impelling these unconscious act-outs isn’t thereby reduced.
  4. So the initiator soon repeats their controlling behavior, stuck in a loop of unresolved feelings.
  5. Since the self-chosen interests of someone who’s being controlled are lesser concerns to the initiator than exercising control, the controlled person may or may not be helped by the controller’s act-outs.

Research provides abundant evidence that we are unique individuals.

This is a strong indicator of who is best qualified to direct each of our unique lives.

A person who is driven to control others’ lives won’t accept epigenetic research as instructive for understanding, honoring, and respecting others as unique individuals. They’ll use research as a way to enable their own unconscious act-outs, and view it as offering opportunities for interventions into the lives of others.

This is the way that “pharmacological agents or social interventions” are often the intended “use of epigenetic and developmental findings.” Interventions receive justifications with “a possible agenda of the social studies of the life-sciences.”

Becoming aware of one’s own act-outs – and then individually addressing one’s own underlying problems – often take backseats to employment and other concerns to keep enabling one’s own behavior. That makes it likely that interventions justified by “epigenetic findings..in social policy” will continue, whether or not the subjects agree that they’re being helped.

For examples, take a look at a few of the YouTube presentations by people employed in the social sciences and social services on a topic of epigenetics. Compare them with the current state of epigenetic research in Grokking an Adverse Childhood Experiences (ACE) score.

What did you notice? How many presentations emphasized disrupted prenatal development – a period when problems can be prevented? Did you instead see that many more of the presentations emphasized controlling behavior?

http://journal.frontiersin.org/article/10.3389/fnhum.2014.00309/full “The social brain meets the reactive genome: neuroscience, epigenetics and the new social biology“

A human study of changes in gene expression

gettingwell4 2-3 stars Required further work, Epigenetics ,

This 2015 international human study of genetic and epigenetic factors was the largest in its field:

“We perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify 1,497 genes that are differentially expressed with chronological age.

We further used the gene expression profiles to calculate the ‘transcriptomic age’ of an individual, and show that differences between transcriptomic age and chronological age are associated with biological features.”

Items of interest:

  • About 1,450 of the “1,497 genes that are differentially expressed” are newly identified;
  • The subjects’ mean age was 55.81 with a pooled standard deviation of 11.59;
  • The mean difference “between transcriptomic age and chronological age” was 7.84 years; and
  • Native American, Mexican American, and African American studies were used as replication cohorts.

It was refreshing to see the peer-review influence of numerous coauthors on the study. Papers that are written by only one or two researchers don’t often have frank limitation explanations such as:

“A potential limitation of our study is that we relied on a linear regression model to identify age-associated genes. A linear model assumes constant change over age, which may not be always correct in biological processes that stretch over several decades (adulthood). A recent study demonstrated that a quadratic regression model has a higher statistical fit to cross-sectional gene expression datasets over linear model.

A limitation of our study is that we used the Illumina Infinium Human Methylation 450K Bead Chip Array for measuring methylation levels: this array queries only 1.6% of all CpGs in the genome and the CpG selection is biased towards CpG islands.

In addition, we did not examine non-CpG methylated sites, which have recently been suggested to play a role in regulating gene expression as well.

Other techniques—whole-genome bisulfite sequencing and methylC-capture (MCC) sequencing, for example—have definite technical advantages (higher resolution and no CpG island selection bias), but these have currently not been applied to a large number of samples.”

http://www.nature.com/ncomms/2015/151022/ncomms9570/full/ncomms9570.html “The transcriptional landscape of age in human peripheral blood”

Transgenerational epigenetic programming with stress and microRNA

gettingwell4 4-5 stars Advanced knowledge, Brain development, Cortisol, Epigenetics, Hypothalamus, Limbic system, Neurochemicals, Stress , , , ,

This 2015 Pennsylvania rodent study found:

“Sperm miRs [microRNAs, a small non-coding RNA that has a role in gene expression] function to reduce maternal mRNA [messenger RNA, a large RNA that carries codes for protein production] stores in early zygotes, ultimately reprogramming gene expression in the offspring hypothalamus and recapitulating the offspring stress dysregulation phenotype.”

These researchers caused stress-induced changes at an early stage of embryonic development with microRNA injections. Resultant adverse effects weren’t observed until subjects were adults!

Most news coverage focused on it being a male’s stress, not a female’s, that affected a developing embryo. Either or both sexes can epigenetically disadvantage a fetus – okay.

Demonstrating how a damaging influence can begin immediately after conception, but symptoms didn’t present until adulthood made this study newsworthy.

Although the term “transgenerational” was used in the study’s title, abstract, and elsewhere, studied epigenetic effects were intergenerational rather than transgenerational. Per A review of epigenetic transgenerational inheritance of reproductive disease, for the term to apply, researchers need to provide evidence in at least the next 2 male or non-gestating female generations and/or 3 gestating female generations of:

“Altered epigenetic information between generations in the absence of continued environmental exposure.”

From a press release, a study coauthor who also coauthored How to make a child less capable even before they are born: stress the pregnant mother-to-be stated:

“Bale suspects that when a male experiences stress it may trigger the release of miRs contained in exosomes from epithelial cells that line the epididymis, the storage and maturation site for sperm between the testes and the vas deferens. These miRs may be incorporated into maturing sperm and influence development at fertilization.”

Not all stress-related gene expression in pituitary and adrenal glands differed.

http://www.pnas.org/content/112/44/13699.full “Transgenerational epigenetic programming via sperm microRNA recapitulates effects of paternal stress”

The roles of DNA methylation and demethylation in forming memories

gettingwell4 2-3 stars Required further work, Anterior cingulate cortex, Brain development, Cerebrum, Epigenetics, Glutamate, Hippocampus, Limbic system, Memory, Neurochemicals , , , ,

This 2015 Alabama combined animal and human review noted:

“Memories can last a lifetime, yet the proteins that enable synaptic plasticity, allowing for the establishment and maintenance of the memory trace, are subject to perpetual turnover.

DNA methylation may likely serve as the principle cellular information storage device capable of stably and perpetually regulating cellular phenotype.”

The authors developed a framework for understanding disparate findings of DNA methylation and demethylation concerning memory.

The dependencies expressed in the framework among the numerous factors – with their relative strengths, timings, and durations – reminded me of this video:

1) If such an error-prone framework accurately reflected the evolved architecture of our memory, we wouldn’t have the variety and number and intensity of memories that we have.

2) The framework neither accounted for prenatal memory processes nor differentiated emotional memories, although some of the referenced studies’ findings were applicable.

3) DNA methylation and demethylation aren’t the entirety of memory formation explanations. For example, they don’t explain state-dependent memories that can be instantiated, reactivated, and amnesia induced without involving “the proteins that enable synaptic plasticity” described in the authors’ framework. For completeness, the authors could have assessed the relative contributions of other memory processes, or at least enumerated them.

4) DNA methylation and demethylation explanations don’t cover all epigenetic biochemical processes. There are also placental interactions, histone/protein interactions, microRNA interactions, etc. For completeness, the authors could have placed the review’s topic within appropriate contexts of other epigenetic processes that influence memory.

This review of DNA methylation and demethylation roles in memory formation opened up a few slats in the blind covering one window. There’s more to be done to fully open that blind, and more window blinds to be opened before the workings of our memory are illuminated.

http://nro.sagepub.com/content/21/5/475.full “DNA Methylation in Memory Formation: Emerging Insights”

A review of the epigenetic basis for mental illness

gettingwell4 4-5 stars Advanced knowledge, Brain development, Cerebrum, Epigenetics, Limbic system, Lower brain, Memory, Stress , , , , ,

This 2015 New York combined animal and human review of epigenetic studies noted:

“While genetic factors are important in the etiology of most mental disorders, the relatively high rates of discordance among identical twins, particularly for depression and other stress-related syndromes, clearly indicate the importance of additional mechanisms.

Environmental factors such as stress are known to play a role in the onset of these illnesses.

Exposure to such environmental insults induces stable changes in gene expression, neural circuit function, and ultimately behavior, and these maladaptations appear distinct between developmental versus adult exposures.

Increasing evidence indicates that these sustained abnormalities are maintained by epigenetic modifications in specific brain regions.”

Placing the “maladaptations” and “sustained abnormalities” phrases into their contexts:

  • A fetus biologically adapted to their environment – however toxic it was – in order to best survive.
  • These adaptations for survival were subsequently viewed as Disrupted Neurodevelopment and “maladaptations” from the perspectives of normal development and environments.
  • The “sustained abnormalities” caused within the earlier environments “are maintained by epigenetic modifications.” An improved environment wasn’t impetus enough to change developmental “maladaptations.”

Per the below link, it’s been a month since this review was published. Why has there been ZERO news coverage of it?

One reason may be that the Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, didn’t issue a press release or otherwise publicize it. Another reason may be the groups that are opposed to its findings:

  • Parents who provided harmful environments for their children, beginning at conception;
  • People who feel threatened when scientific causal evidence resonates with what happened in their own lives, and in response, limit their empathetic understanding of others’ problems;
  • Social workers, psychologists, and others in industries whose paychecks depend on efforts that aren’t directed towards ameliorating the causes for these later-life effects;
  • Psychiatrists and medical personnel whose livelihoods depend on pharmaceutical and other treatments that only alleviate symptoms;
  • Researchers whose funding depends on producing non-etiologic findings.

Despite resistance to this review’s findings, a large number of people would benefit from publicizing evidence for:

“These sustained abnormalities are maintained by epigenetic modifications in specific brain regions.”

http://nro.sagepub.com/content/early/2015/09/24/1073858415608147 “Epigenetic Basis of Mental Illness”

Genetic causes for epigenetic symptoms

gettingwell4 4-5 stars Advanced knowledge, Brain development, Epigenetics, Hippocampus, Limbic system, Memory , , , , , , ,

This 2015 human summary study was of 44 genetic disorders that disrupt the maintenance of epigenetic modifications:

“..making them likely to have significant downstream epigenetic consequences. Interestingly, these patients often demonstrate neurological dysfunction, suggesting that precise epigenetic regulation may be critical for neuronal homeostasis. However, at the same time, it is important to keep in mind that many of these proteins have additional non-epigenetic roles.

Mutations in many of these components have now been linked to a number of well-known causes of intellectual disability. Intellectual disability is generally defined as deficits of intellectual function and adaptive behavior that occur during the developmental period.

Given the opposing activity of many of the components of the epigenetic machinery, the pathogenic sequence in these disorders involves an imbalance of chromatin states. Keeping a subset of genes under “pressure” from two opposing systems may allow the cellular system to rapidly respond to environmental stimuli.

These disorders, on average, have unusual phenotypic breadth. Similarly, there is a shift in distribution toward a higher number of organ systems affected.

In addition to developmental phenotypes (multiple congenital anomalies), in some cases there appear to be ongoing defects that remain consequential in post-natal life. An example of the latter is the hippocampal memory defects seen in many of the mouse models.

This raises the question whether cells undergoing neurogenesis and synaptogenesis are particularly sensitive to subtle defects of the epigenetic machinery and downstream epigenetic abnormalities. A major remaining question is whether neurogenesis defects and/or abnormalities of synaptic plasticity are a unifying pathophysiological process.”

The researchers represented the 44 genetic disorders on a wheel graph:

F1.large

I look forward to further research that includes non-genetic disruptors of epigenetic modifications.

http://genome.cshlp.org/content/25/10/1473.full “The Mendelian disorders of the epigenetic machinery”

Identifying epigenetic DNA changes with blood tests

gettingwell4 2-3 stars Required further work, Epigenetics , ,

This 2015 Chinese human study found:

“With reference to methylation profiles of different tissues, we developed a general approach for studying the major tissue contributors to the circulating DNA pool. This development has opened up numerous research avenues and diagnostic applications.

Our study takes advantage of the recent availability of reference methylomes of a number of tissues. It is likely that such reference databases would be continually updated to include more sample types and from more individuals.”

Up to 41% of plasma DNA in pregnant women was from the placenta. However, I didn’t understand why the non-pregnant women in the control group had measurable placental DNA of up to 2.9%. Maybe it was leftover from a prior pregnancy?

http://www.pnas.org/content/112/40/E5503.full “Plasma DNA tissue mapping by genome-wide methylation sequencing for noninvasive prenatal, cancer, and transplantation assessments”

Leaky gates, anxiety, and grocery store trips without buying list items

gettingwell4 4-5 stars Advanced knowledge, Brain development, Brainstem, Cerebrum, Cortisol, Dopamine, Epigenetics, Limbic system, Lower brain, Memory, Neurochemicals, Oxytocin, Primal Therapy, Serotonin, Stress , , , , , , , ,

An interview with Jeff Link, the editor of Dr. Arthur Janov’s 2011 book “Life Before Birth: The Hidden Script that Rules Our Lives” with Ken Rose:

“Even further confirmation for some of the views of Janov, that maybe weren’t widely accepted for a time, it’s new research now being done into memory and what a lot of scientist are seeing, a lot of different studies is that memory reactivates the same neuroimpulses that were initially firing off when the event happened.

So a traumatic event when you remember it, the act of remembering it is actually creating a neuromirror of what went on initially.

In a lot of ways that is what Primal Therapy is attempting to do; is to go back to that place and reconnect, or as it’s sometimes referred to, reconsolidate the brain state so that real healing can take place.”

Transcript (part 4 of 6): http://cigognenews.blogspot.com/2015/09/ken-rose-on-life-before-birth-part-46.html

MP3: http://www.pantedmonkey.org/podcastgen/download.php?filename=2011-12-15_1300_what_now_jeff_link.mp3

Genetic statistics don’t necessarily predict the effects of an individual’s genes

gettingwell4 4-5 stars Advanced knowledge, Epigenetics

I curated this 2015 Howard Hughes Medical Institute rodent study of DNA methylation because of the reason driving the researchers’ efforts:

“Epigenomic analyses are limited by averaging of population-wide dynamics and do not inform behavior of single cells. We observe dynamics at the single-cell level not predicted by epigenomic analysis.”

This rationale was also the driving force behind the Is what’s true for a population what’s true for an individual? study and its companion Changing an individual’s future behavior even before they’re born. The methodology of genome-wide association studies (GWAS) usually:

“Focuses on the average effect of alternative alleles averaged in a population.”

What this methodology often missed was:

“When phenotypic variation results from alleles that modify phenotypic variance rather than the mean, this link between genotype and phenotype will not be detected.”

Population-wide epigenetic statistics don’t necessarily inform us about the epigenetic activities and attributes of an individual’s genes, even down at the single-cell level.

http://www.pnas.org/content/112/31/E4216.full “The Xist RNA-PRC2 complex at 20-nm resolution reveals a low Xist stoichiometry and suggests a hit-and-run mechanism in mouse cells”

Using epigenetic DNA methylation markers to estimate biological age

gettingwell4 < 0 Detracted from science, Epigenetics, Stress, Telomeres

I curated this 2015 Georgia human study only for its use of two methods of estimating biological age. The researchers misguidedly used these techniques to help paint a scientific patina on an agenda.

One of the methods was originated by a coauthor of The degree of epigenetic DNA methylation may be used as a proxy to measure biological age study. He compared his epigenetic clock technique with the other technique here:

  • His technique used the same 353 DNA regions (CpGs, cytosine and guanine separated by only one phosphate link) across different tissues to compare tissue/organ ages;

  • “The DNA methylation levels of 193 of these markers increase with age but the remaining 160 markers show the opposite behavior.”

  • His technique had a Pearson correlation coefficient of r=0.96 with chronological age in this 2013 study;
  • The other technique:

    “Works poorly for blood samples from subjects who are younger than 20.”

That such methods were available calls into question why the researchers of A study of biological aging in young adults with limited findings didn’t avail themselves of these techniques. They used techniques that were less informative such as telomere length. As an example of how that study’s methods were known to be limited, this 2009 study found that the correlation between chronological age and telomere length was r = −0.51 in women and r = −0.55 in men.

http://www.pnas.org/content/112/33/10325.full “Self-control forecasts better psychosocial outcomes but faster epigenetic aging in low-SES youth”

A study of biological aging in young adults with limited findings

gettingwell4 0-1 star Wasted resources, Epigenetics, Telomeres ,

This 2015 New Zealand human study used the same subjects of the More from the researchers that found people have the same personalities at age 26 that they had at age 3 study. These researchers used 10 biologic age markers of subjects at age 38 to find that their biological ages ranged from 28 to 61.

F2.large

Researchers assessed subjects’ pace of aging at ages 26, 32, and 38 with 11 more biomarkers, including leukocyte telomere length. Three of the initial 10 biomarkers weren’t used because measurements were taken only at age 38.

These researchers also assessed physical functioning, physical limitations, cognitive testing, retinal imaging, self-rated health, and facial aging. There was a fascinating graph in the supplementary material of the effect on each of these assessments of successively leaving out each of 18 pace-of-aging biomarkers.

There were three areas I expected to see covered that weren’t addressed in this study:

  1. Where were links back to all relevant measurements and predictions made when these subjects were ages 3, 5, 7..? Other studies of these same subjects made such links, but only cognitive testing was linked back in this study. Were these researchers trying to pretend that these dramatic later-life physical measurements weren’t effects of earlier-life causes?
  2. Where were psychological measurements? Are we to believe that subjects’ states of mind had no relationships to their biomarkers?
  3. I didn’t see any effort to use newer measures such as The degree of epigenetic DNA methylation may be used as a proxy to measure biological age study. I’d expect that these subjects’ historical tissue samples were available. The peer reviewer certainly was familiar with newer biomarkers.

http://www.pnas.org/content/112/30/E4104.full “Quantification of biological aging in young adults”

Stress in early life can alter physiology and behavior across the entire lifespan

gettingwell4 4-5 stars Advanced knowledge, Amygdala, Brain development, Cerebrum, Cortisol, Epigenetics, Hippocampus, Immune system, Limbic system, Memory, Neurochemicals, Stress, Testosterone , , , , , , , ,

I’ll quote a few sections of this 2014 summary of 111 studies concerning stress, including the authors’ research:

“The brain is the central organ of stress and adaptation to stressors because:

  • It not only perceives what is threatening or potentially threatening and initiates behavioral and physiological responses to those challenges,
  • But also is a target of the stressful experiences and the hormones and other mediators of the stress response.

The stress history of parents is a significant factor in the resilience of their offspring.

Environmental stress transduces its effects into lasting changes on physiology and behavior, which can vary even among genetically identical individuals.

Stress in early life can alter physiology and behavior across the entire lifespan.

Structural stress memory is even more apparent with regard to gene expression in stress-sensitive brain regions like the hippocampus.

Individual history is important and that there is a memory of stress history retained by neurons at the cellular level in regions like the hippocampus.

Stress has a number of known effects on epigenetic marks in the brain, producing alterations in DNA methylation and histone modifications in most of the stress-sensitive brain regions examined, including the hippocampus, amygdala, and prefrontal cortex.”

It seemed to be taboo to note that most of – and the largest of – detrimental effects of stress occurred during womb-life in the mother’s environment. The authors instead opted for a politically correct “the stress history of parents” phrase.

Referenced studies had findings relevant to the earliest periods of life, including Figure 1:

interactions

“Those organs that show the highest levels of retrotransposon [a repeat element (mobile DNA sequences often involved in mutations) type formed by copy-and-paste mechanisms] activity, such as the brain and placenta, also seem to be both steroidogenic and steroid-sensitive.”

However, Figure 1 was given a beneficial context, and other studies’ findings weren’t mentioned in their contexts of detrimental effects on fetuses of mothers who were stressed while pregnant.

http://www.pnas.org/content/112/22/6828.full “Stress and the dynamic genome: Steroids, epigenetics, and the transposome”

Is what’s true for a population what’s true for an individual?

gettingwell4 5+ stars Premium, Epigenetics , ,

This 2015 Harvard fruit fly study found:

“Genetically identical individuals display variability in their behaviors even when reared in essentially identical environments.

Individual flies exhibit significant bias in their left vs. right locomotor choices during exploratory locomotion.”

Here’s an example of why population statistics such as in GWAS didn’t necessarily apply to an individual:

“The probability of turning right averaged across all individuals within each line was statistically indistinguishable from 50%. However, an individual fly’s probability of turning right often diverged markedly from the population average.

For example, nearly one quarter (23.5%) of CS [Canton-S] flies turned right greater than 70% of the time or less than 30% of the time. This distribution would be unlikely indeed if all flies were choosing to turn right with identical probabilities.”

The researchers noted other species with similar findings:

“Individuals can develop idiosyncratic behaviors, morphology, and gene expression profiles. For example, stochastic DNA methylation may contribute to phenotypic variation that is uncorrelated to genetic variation.”

This study should inform other studies such as the Separating genetic from environmental factors when assessing educational achievement, to the degree its findings apply to humans.

As the findings applied to neurological areas:

“The magnitude of locomotor handedness is under the control of neurons within a brain region implicated in motor planning and execution.”

I was surprised that the study’s news coverage included this opinion:

“They are suggesting that variation [read: individuality] itself might be a genetic trait.”

The researchers stated their case in the companion study Changing an individual’s future behavior even before they’re born.

http://www.pnas.org/content/112/21/6700.full “Neuronal control of locomotor handedness in Drosophila”

Separating genetic from environmental factors when assessing educational achievement

gettingwell4 0-1 star Wasted resources, Brain development, Epigenetics , ,

This 2014 UK study of identical and fraternal twins found that an average of 62% of the differences among their scores on a significant test given at age 16 were due to genetic factors:

“Genetic influence is greater for achievement than for intelligence, and other behavioral traits are related to educational achievement largely for genetic reasons.”

However, the “genetic reasons” term didn’t mean that the researchers actually took genetic samples. From one news article:

“Identical twins share 100 percent of their genes while non-identical twins share just 50 percent of their genes. Because these sets of twins share the same environment, the scientists were able to compare identical and non-identical twins to estimate the relative contributions of genetic and environmental factors.”

This estimation method produced an artificial divide between genetic and environmental factors. Identical twins start out sharing 100% of their genes, but then their genes become expressed differently – often because of environmental factors – to produce unique individuals even before birth.

The sets of identical twins were definitely not the 100% same genetic makeup between themselves at age 16 as they were at conception, and that assumption was the foundation of the researchers’ model:

F2

“Bivariate estimates for additive genetic (A), shared environmental (C), and nonshared environmental (E) contributions to the correlations between GCSE and nine predictors. The total length of the bar indicates the phenotypic correlations.”

The researchers didn’t provide evidence that “genetic reasons” were causal factors to the stated extent. Although the model’s numbers may have indicated that the method’s results were valid, that didn’t necessarily mean that the reality of genetic and epigenetic influences on the subjects were represented to the stated precision by the results.

The weather analogy of Scientific evidence applies to this study’s methods:

“We can think about what we mean by evidence. For example, that when you see dark storm clouds overhead, that’s strong evidence that it’s about to rain. If you smell a certain scent, that’s maybe weak evidence that it’s about to rain. And if we see the dark storm clouds and then we smell the scent, the evidence doesn’t get weaker: if anything, it gets stronger.

But P-values in a circumstance like that, where you have a very small P-value in one dataset and a not-so-small P-value in a second dataset, you put the data together and the P-value will tend to sort of average.

So the P-value is not behaving like evidence.”

Better methods of estimating “the relative contributions of genetic and environmental factors” are available with actual genetic sampling. One way is to measure the degree of DNA methylation of genes as did:

The study and its news coverage were full of politically-correct buzzwords – for example, the researchers’ statement:

“The results also support the trend in education toward personalized learning.”

This “personalized learning” is a teacher not telling a student:

“You’re doing poorly at math. You need to pay attention in class and do the homework.”

but instead saying:

“You have a different learning style. We’ll tailor the math lessons to your style.”

The funniest thing I saw in the study’s news coverage was this one where someone argued that the researchers were wrong and that they needed educational psychologists on their staff to interpret the data. Guess the profession of the arguer!

http://www.pnas.org/content/111/42/15273.full “The high heritability of educational achievement reflects many genetically influenced traits, not just intelligence”