How to hijack science: Ignore its intent and focus on the 0.0001%

This 2018 Belgian review hijacked science to further an agenda:

“We addressed this issue at the LATSIS Symposium ‘Transgenerational Epigenetic Inheritance: Impact for Biology and Society’, in Zürich, 28–30 August 2017, and here provide important arguments why environmental and lifestyle-related exposures in young men should be studied.”

The reviewer DETRACTED from science in the studied area – transgenerational epigenetic inheritance – by ignoring its intent. As shown by A self-referencing study of transgenerational epigenetic inheritance which I also curated today, the purpose of such animal studies is to find the mechanisms in order to help humans.


Putting that study’s graphic into human terms, F3 male great-grandchildren may be adversely affected by their F0 great-grandmothers being poisoned while pregnant with their F1 grandfathers, who – with their F2 fathers – may have also been adversely affected.


What the reviewer asserted without proof:

“The importance of maternal lifestyle, diet and other environmental exposures before and during gestation period is well recognized.”

is NOT TRUE for the studied area.

The evidence disproving this assertion is that NO HUMAN STUDIES scientifically demonstrating causes for transgenerational epigenetic inheritance effects have been published!

EVER!!

There’s a huge gap between “The importance..is well recognized” of anything regarding transgenerational epigenetic inheritance and ZERO human studies.

Why has no one published scientifically adequate human evidence to demonstrate “Transgenerational Epigenetic Inheritance: Impact for Biology and Society” effects on ALL of the F1, F2, and F3 human generations as consequences “of maternal lifestyle, diet and other environmental exposures before and during gestation period?” What are we waiting for?

The reviewer said “young men should be studied” but said nothing about resolving bottlenecks in funding human research of the studied area. Do researchers even have opportunities to make a NON-AGENDA-DRIVEN difference in this field?

With ZERO published human studies, transgenerational epigenetic inheritance research can’t be recharacterized into a female vs. male agenda. The reviewer’s attempt to do so diminished the importance of research into human critical development periods.

This agenda’s viewpoint ignored human correlates of evidence from animal studies like The lifelong impact of maternal postpartum behavior:

“The defect in maternal care induced by gestational stress programs the development of the offspring.”

Will the reviewer’s suggested interventions – such as changing an adult’s lifestyle a long time after their development was altered – somehow make up for what went wrong early in their life, even before they were born?

With the evidence from animal studies such as:

is there any doubt that similar mechanisms may be involved in humans, and that human phenotypes may likewise be intergenerationally and/or transgenerationally transmitted?

The reviewer asserted:

“Studying humans is challenging, because of ethical reasons”

But do “ethical reasons” prohibit non-instigating human studies of stress, the intergenerationally and transgenerationally transmitted effects of which seem to be ubiquitous among humans?

In The Not-Invented-Here syndrome I pointed out another problem that the reviewer’s agenda is less than helpful in resolving:

“How can animal studies like the current study help humans when their models don’t replicate common human conditions? This failure to use more relevant models has follow-on effects such as human intergenerational and transgenerational epigenetic inheritance being denigrated due to insufficient evidence.”


I’ll repeat What is a father’s role in epigenetic inheritance? in closing:

“The review focused on 0.0001% of the prenatal period for what matters with the human male – who he was at the time of a Saturday night drunken copulation – regarding intergenerational and transgenerational epigenetic inheritance of metabolic diseases.

The human female’s role – who she was at conception AND THEN what she does or doesn’t do during the remaining 99.9999% of the prenatal period to accommodate the fetus and prevent further adverse epigenetic effects from being intergenerationally and transgenerationally transmitted – wasn’t discussed.

Who benefits from this agenda’s narrow focus?”

https://academic.oup.com/eep/article/4/2/dvy007/4987171 “POHaD: why we should study future fathers”

Resiliency in stress responses

This 2018 US Veterans Administration review subject was resiliency and stress responses:

Neurobiological and behavioral responses to stress are highly variable. Exposure to a similar stressor can lead to heterogeneous outcomes — manifesting psychopathology in one individual, but having minimal effect, or even enhancing resilience, in another.

We highlight aspects of stress response modulation related to early life development and epigenetics, selected neurobiological and neurochemical systems, and a number of emotional, cognitive, psychosocial, and behavioral factors important in resilience.”

The review cited studies I’ve previously curated:


There were two things I didn’t understand about this review. The first was why the paper isn’t freely available. It’s completely paid for by the US taxpayer, and no copyright is claimed. I recommend contacting the authors for a copy.

The second was why the VA hasn’t participated in either animal or human follow-on studies to the 2015 Northwestern University GABAergic mechanisms regulated by miR-33 encode state-dependent fear. That study’s relevance to PTSD, this review’s subject, and the VA’s mission is too important to ignore. For example:

“Fear-inducing memories can be state dependent, meaning that they can best be retrieved if the brain states at encoding and retrieval are similar.

“It’s difficult for therapists to help these patients,” Radulovic said, “because the patients themselves can’t remember their traumatic experiences that are the root cause of their symptoms.”

The findings imply that in response to traumatic stress, some individuals, instead of activating the glutamate system to store memories, activate the extra-synaptic GABA system and form inaccessible traumatic memories.”

I curated the research in A study that provided evidence for basic principles of Primal Therapy. These researchers have published several papers since then. Here are the abstracts from three of them:

Experimental Methods for Functional Studies of microRNAs in Animal Models of Psychiatric Disorders

“Pharmacological treatments for psychiatric illnesses are often unsuccessful. This is largely due to the poor understanding of the molecular mechanisms underlying these disorders. We are particularly interested in elucidating the mechanism of affective disorders rooted in traumatic experiences.

To date, the research of mental disorders in general has focused on the causal role of individual genes and proteins, an approach that is inconsistent with the proposed polygenetic nature of these disorders. We recently took an alternative direction, by establishing the role of miRNAs in the coding of stress-related, fear-provoking memories.

Here we describe in detail our work on the role of miR-33 in state-dependent learning, a process implicated in dissociative amnesia, wherein memories formed in a certain brain state can best be retrieved if the brain is in the same state. We present the specific experimental approaches we apply to study the role of miRNAs in this model and demonstrate that miR-33 regulates the susceptibility to state-dependent learning induced by inhibitory neurotransmission.”

Neurobiological mechanisms of state-dependent learning

“State-dependent learning (SDL) is a phenomenon relating to information storage and retrieval restricted to discrete states. While extensively studied using psychopharmacological approaches, SDL has not been subjected to rigorous neuroscientific study.

Here we present an overview of approaches historically used to induce SDL, and highlight some of the known neurobiological mechanisms, in particular those related to inhibitory neurotransmission and its regulation by microRNAs (miR).

We also propose novel cellular and circuit mechanisms as contributing factors. Lastly, we discuss the implications of advancing our knowledge on SDL, both for most fundamental processes of learning and memory as well as for development and maintenance of psychopathology.”

Neurobiological correlates of state-dependent context fear

“Retrieval of fear memories can be state-dependent, meaning that they are best retrieved if the brain states at encoding and retrieval are similar. Such states can be induced by activating extrasynaptic γ-aminobutyric acid type A receptors (GABAAR) with the broad α-subunit activator gaboxadol. However, the circuit mechanisms and specific subunits underlying gaboxadol’s effects are not well understood.

Here we show that gaboxadol induces profound changes of local and network oscillatory activity, indicative of discoordinated hippocampal-cortical activity, that were accompanied by robust and long-lasting state-dependent conditioned fear. Episodic memories typically are hippocampus-dependent for a limited period after learning, but become cortex-dependent with the passage of time.

In contrast, state-dependent memories continued to rely on hippocampal GABAergic mechanisms for memory retrieval. Pharmacological approaches with α- subunit-specific agonists targeting the hippocampus implicated the prototypic extrasynaptic subunits (α4) as the mediator of state-dependent conditioned fear.

Together, our findings suggest that continued dependence on hippocampal rather than cortical mechanisms could be an important feature of state-dependent memories that contributes to their conditional retrieval.”


Here’s an independent 2017 Netherlands/UC San Diego review that should bring these researchers’ efforts to the VA’s attention:

MicroRNAs in Post-traumatic Stress Disorder

“Post-traumatic stress disorder (PTSD) is a psychiatric disorder that can develop following exposure to or witnessing of a (potentially) threatening event. A critical issue is to pinpoint the (neuro)biological mechanisms underlying the susceptibility to stress-related disorder such as PTSD, which develops in the minority of ~15% of individuals exposed to trauma.

Over the last few years, a first wave of epigenetic studies has been performed in an attempt to identify the molecular underpinnings of the long-lasting behavioral and mental effects of trauma exposure. The potential roles of non-coding RNAs (ncRNAs) such as microRNAs (miRNAs) in moderating or mediating the impact of severe stress and trauma are increasingly gaining attention. To date, most studies focusing on the roles of miRNAs in PTSD have, however, been completed in animals, using cross-sectional study designs and focusing almost exclusively on subjects with susceptible phenotypes.

Therefore, there is a strong need for new research comprising translational and cross-species approaches that use longitudinal designs for studying trajectories of change contrasting susceptible and resilient subjects. The present review offers a comprehensive overview of available studies of miRNAs in PTSD and discusses the current challenges, pitfalls, and future perspectives of this field.”

Here’s a 2017 Netherlands human study that similarly merits the US Veterans Administration’s attention:

Circulating miRNA associated with posttraumatic stress disorder in a cohort of military combat veterans

“Posttraumatic stress disorder (PTSD) affects many returning combat veterans, but underlying biological mechanisms remain unclear. In order to compare circulating micro RNA (miRNA) of combat veterans with and without PTSD, peripheral blood from 24 subjects was collected following deployment, and isolated miRNA was sequenced.

PTSD was associated with 8 differentially expressed miRNA. Pathway analysis shows that PTSD is related to the axon guidance and Wnt signaling pathways, which work together to support neuronal development through regulation of growth cones. PTSD is associated with miRNAs that regulate biological functions including neuronal activities, suggesting that they play a role in PTSD symptomatology.”


See the below comments for reasons why I downgraded this review’s rating.

https://link.springer.com/article/10.1007/s11920-018-0887-x “Stress Response Modulation Underlying the Psychobiology of Resilience” (not freely available)

Faith-tainted epigenetics

This 2018 Loma Linda review subject was epigenetic interventions for aging:

“Epigenomic markers of aging, global DNA hypomethylation and promoter-specific hypermethylation may be engendered by iron and HCys [homocysteine] retention.

MiR-29/p53 axis may reverse age-related methylomic shifts, stabilizing both the genome and the epigenome, therefore removing a major risk factor of neurodegeneration. Lowering iron and HCys overload can be accomplished via chelation, blood donation and maintaining an adequate omega-6/omega-3 ratio.”


Sometimes it’s difficult to detect researchers’ biases. If a reader didn’t know about the funding sponsor’s mission:

“Each day we seek to extend the teaching and healing ministry of Jesus Christ”

they may view this paper as unbiased rather than as a directed narrative.

Consider the sponsor’s influence from the perspective of someone seeking treatment for Alzheimer’s disease. If a doctor in this review sponsor’s hospital system recommended chelation treatment, hope would be generated for the patient. Adopting the doctor’s belief about the treatment, though, would be contrary to other evidence per this review:

“In 2008, the NIH chelation trial stopped enrolling patients, approximately two years early.

There is no indication for exposing patients with dementia to the risks of chelation therapy because current chelators cannot help them.”

After reading another review that had this sponsor – The lack of oxygen’s epigenetic effects on a fetus – which also reflected the influence of the sponsor’s biases, and had a directed narrative that ignored evidence contradicting the narrative, and involved storytelling, I’m done curating any paper sponsored by this institution.

http://www.nrronline.org/downloadpdf.asp?issn=1673-5374;year=2018;volume=13;issue=4;spage=635;epage=636;aulast=Sfera;type=2 “Epigenetic interventions for brain rejuvenation: anchoring age-related transposons” (click the pdf button)

Manufacturing PTSD evidence with machine learning

What would you do if you were a scientist who had strong beliefs that weren’t borne out by experimental evidence?

Would you be honest with yourself about the roots of the beliefs? Would you attempt to discover why the beliefs were necessary for you, and what feelings were associated with the beliefs?

Instead of the above, the researchers of this 2017 New York human study reworked negative findings of two of the coauthors’ 2008 study until it fit their beliefs:

“The neuroendocrine response contributes to an accurate predictive signal of PTSD trajectory of response to trauma. Further, cortisol provides a stable predictive signal when measured in conjunction with other related neuroendocrine and clinical sources of information.

Further, this work provides a methodology that is relevant across psychiatry and other behavioral sciences that transcend the limitations of commonly utilized data analytic tools to match the complexity of the current state of theory in these fields.”


1. The limitations section included:

“It is important to note that ML [machine learning]-based network models are an inherently exploratory data analytic method, and as such might be seen as ‘hypotheses generating’. While such an approach is informative in situations where complex relationships cannot be proposed and tested a priori, such an approach also presents with inherent limitations as a high number of relationships are estimated simultaneously introducing a non-trivial probability of false discovery.”

2. Sex-specific impacts of childhood trauma summarized why cortisol isn’t a reliable biological measurement:

“Findings are dependent upon variance in extenuating factors, including but not limited to, different measurements of:

  • early adversity,
  • age of onset,
  • basal cortisol levels, as well as
  • trauma forms and subtypes, and
  • presence and severity of psychopathology symptomology.”

Although this study’s authors knew or should have known that review’s information, cortisol was the study’s foundation, and beliefs in its use as a biomarker were defended.

3. What will it take for childhood trauma research to change paradigms? described why self-reports of childhood trauma can NEVER provide direct evidence for trauma during the top three periods when humans are most sensitive to and affected by trauma:

The basic problem prohibiting the CTQ (Childhood Trauma Questionnaire) from discovering likely most of the subjects’ historical traumatic experiences that caused epigenetic changes is that these experiences predated the CTQ’s developmental starting point.

Self-reports were – at best – evidence of experiences after age three, distinct from the experience-dependent epigenetic changes since conception.”

Yet the researchers’ beliefs in the Trauma History Questionnaire’s capability to provide evidence for early childhood traumatic experiences allowed them to make such self-reports an important part of this study’s findings, for example:

“The reduced cortisol response in the ER [emergency room] was dependent on report of early childhood trauma exposure.”

https://www.nature.com/articles/tp201738 “Utilization of machine learning for prediction of post-traumatic stress: a re-examination of cortisol in the prediction and pathways to non-remitting PTSD”

Sleep and adult brain neurogenesis

This 2018 Japan/Detroit review subject was the impact of sleep and epigenetic modifications on adult dentate gyrus neurogenesis:

“We discuss the functions of adult‐born DG neurons, describe the epigenetic regulation of adult DG neurogenesis, identify overlaps in how sleep and epigenetic modifications impact adult DG neurogenesis and memory consolidation..

Whereas the rate of DG neurogenesis declines exponentially with age in most mammals, humans appear to exhibit a more modest age‐related reduction in DG neurogenesis. Evidence of adult neurogenesis has also been observed in other regions of the mammalian brain such as the subventricular zone, neocortex, hypothalamus, amygdala, and striatum.

Adult‐born DG neurons functionally integrate into hippocampal circuitry and play a special role in cognition during a period of heightened excitability and synaptic plasticity occurring 4–6 weeks after mitosis. Adult DG neurogenesis is regulated by a myriad of intrinsic and extrinsic factors, including:

  • drugs,
  • diet,
  • inflammation,
  • physical activity,
  • environmental enrichment,
  • stress, and
  • trauma.”


Some of what the review stated was contradicted by other evidence. For example, arguments for sleep were based on the memory consolidation paradigm, but evidence against memory consolidation wasn’t cited for balanced consideration.

It reminded me of A review that inadvertently showed how memory paradigms prevented relevant research. That review’s citations included a study led by one of those reviewers where:

“The researchers elected to pursue a workaround of the memory reconsolidation paradigm when the need for a new paradigm of enduring memories directly confronted them!”

Some of what this review stated was speculation. I didn’t quote any sections after:

 “We go one step further and propose..”

The review also had a narrative directed toward:

“Employing sleep interventions and epigenetic drugs..”

It’s storytelling rather than pursuing the scientific method when reviewers approach a topic as these reviewers did.

Instead of reading a directed narrative, read this informative blog post from a Canadian researcher. The post provided scientific contexts to summarize what was and wasn’t known in 2018 about human neurogenesis.

http://onlinelibrary.wiley.com/doi/10.1002/stem.2815/epdf “Regulatory Influence of Sleep and Epigenetics on Adult Hippocampal Neurogenesis and Cognitive and Emotional Function”

Obtaining convictions with epigenetic statistics?

This 2018 Austrian review subject was forensic applications of epigenetic clock methodologies:

“The methylation-sensitive analysis of carefully selected DNA markers (CpG sites) has brought the most promising results by providing prediction accuracies of ±3–4 years, which can be comparable to, or even surpass those from, eyewitness reports. This mini-review puts recent developments in age estimation via (epi)genetic methods in the context of the requirements and goals of forensic genetics and highlights paths to follow in the future of forensic genomics.”


The point of forensic analysis techniques should be to find the truth about an individual. Doesn’t the principle of “All presumptive evidence of felony should be admitted cautiously; for the law holds it better that ten guilty persons escape, than that one innocent party suffer” still hold?

The methods’ limitations weren’t discussed. Here are some concepts not mentioned in the review:

1) Summary statistics that describe a group or population NEVER necessarily describe an individual member.

For an epigenetic clock methodology example, take a look at Figure 2A in Using an epigenetic clock to assess liver disease. 16 of the 18 individual age acceleration estimates of the control group subjects aren’t close to the median value!

2) The reviewer outlined basic DNA methylation analysis:

“The most commonly pursued approach for analysing CpG sites is sequence analysis of bisulfite-converted DNA, during which single-stranded genomic DNA is treated with sodium bisulfite that deaminates unmethylated cytosine to uracil, while methylated cytosine remains unaffected.

With increasing age, not only genome-wide DNA hypomethylation has been observed but also regional DNA hypermethylation of CpG islands.”

The basic limitation of this analysis wasn’t mentioned, but A study of DNA methylation and age said:

“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.

3) Another omission was that the numbers and types of targets in the discussed DNA methylation technique were severely limited per The primary causes of individual differences in DNA methylation are environmental factors:

“A main limitation with studies using the Illumina 450 K array is that the platform only covers ~1.5 % of overall genomic CpGs, which are biased towards promoters and strongly underrepresented in distal regulatory elements, i.e., enhancers.

The reviewer didn’t provide convincing justifications for using gene expression profiling to obtain convictions. Was it too much to expect a mini-review to offer a balanced view of using epigenetic age estimation in forensic analyses?

https://www.karger.com/Article/FullText/486239 “Age Estimation with DNA: From Forensic DNA Fingerprinting to Forensic (Epi)Genomics: A Mini-Review”

Science and technology hijacked by woo

I’m an avid reader of science articles, abstracts, studies, and reviews. I tried a free subscription to Singularity Hub for a few weeks last month because it seemed to be a suitable source of articles on both science and technology.

I unsubscribed after being disappointed by aspects of science and technology hijacked almost on a daily basis into the realm of woo. Discovering scientific truths and realizing technologies is inspiring enough to stand on its own. It’s sufficiently interesting to publish well-written articles on the process and results.

I was dismayed that the website didn’t host a feedback mechanism for the authors’ articles. We shield ourselves from information incongruent with our beliefs. It’s a problem when a publisher of science and technology articles similarly disallows non-confirming evidence as a matter of policy.

An article may or may not advance knowledge of the subject, and Singularity Hub enables author hubris in presenting their views as the final word on the subject. Directing readers elsewhere for discussion is self-defeating in that every publisher’s goals include keeping visitors on their website as long as possible.

Here’s my feedback on two articles that inappropriately bent reality.


Regarding What Is It That Makes Humans Unique?:

“This trait [symbolic abstract thinking] not only gives us the ability to communicate symbolically, it also allows us to think symbolically, by allowing us to represent all kinds of symbols (including physical and social relationships) in our minds, independent of their presence in the physical world. As a result, internal associations of novel kinds become possible.”

Why limit discussion of our capability for symbolic representations? Other features to explore are:

  1. Aren’t beliefs also products of symbolic abstract thinking?
  2. What attributes of human behavior provide evidence for hopes and beliefs as symbolic representations?
  3. What’s the evolved functional significance that benefits humans of using symbolic abstract thinking to develop hopes and beliefs?

“Our revolutionary traits stand out even more when we take a cosmic perspective..We are not only in the universe, but the universe is also within us..Our brains, as an extension of the universe, are now being used to understand themselves.”

This article should be written well enough to inspire without resorting to unevidenced assertions about revolutions, the cosmos, and the timing of brain functionality.

“Some of us possess higher consciousness than others. The question that we now have to ask ourselves is, how do we cultivate higher consciousness, structural building, and symbolic abstract thinking among the masses?”

What’s the purpose of steering an evolution topic into elitism?


How a Machine That Can Make Anything Would Change Everything received >53,000 views compared with <5,000 views of the above article. This was an indicator that readers of Singularity Hub are relatively more interested in the possible implications of future technology than those of our past biological evolution. Why?

“If nanofabricators are ever built, the systems and structure of the world as we know them were built to solve a problem that will no longer exist.”

We are to believe that we’ll soon have the worldwide solution to problems in food supply, energy supply, medicine availability, income, knowledge – all that’s needed for survival? Should we develop hopes that technology will be our all-providing savior? Hope sells, without a doubt, but why would Singularity Hub mix that in with science?

This article reminded me of the chip-in-the-brain article referenced in Differing approaches to a life wasted on beliefs. Both articles seemingly appealed to future prospects, but the hope aspect showed that the appeals were actually reactions to the past.

If we individually address the impacts of past threats to survival – that include beliefs about future survival – each of us can break out of these self-reinforcing, life-wasting loops. Otherwise, an individual’s thoughts, feelings, and behavior are stuck in reacting to their history, with hopes and beliefs being among the many symptoms.

“Human history will be forever divided in two. We may well be living in the Dark Age before this great dawn. Or it may never happen. But James Burke, just as he did over forty years ago, has faith.”

Is it inspiring that the person mentioned has had a forty-year career of selling beliefs in technology?

Yes, future technologies have promise. Authors can write articles that provide developments without soiling the promise with woo.


This post has somehow become a target for spammers, and I’ve disabled comments. Readers can comment on other posts and indicate that they want their comment to apply here, and I’ll re-enable comments.

What is a father’s role in epigenetic inheritance?

The agenda of this 2017 Danish review was to establish a paternal role in intergenerational and transgenerational epigenetic inheritance of metabolic diseases:

“There are four windows of susceptibility which have major importance for epigenetic inheritance of acquired paternal epigenetic changes:

  1. paternal primordial germ cell (PGC) development,
  2. prospermatogonia stages,
  3. spermatogenesis, and
  4. during preimplantation.”

The review was a long read as the authors discussed animal studies. When it came to human studies near the paper’s end, though, the tone was of a “we know this is real, we just have to find it” variety. The authors acknowledged:

“To what extent the described DNA methylation changes influence the future health status of offspring by escaping remodeling in the preimplantation period as well as in future generations by escaping remodeling in PGC remodeling has yet to be determined.

These studies have not yet provided an in-depth understanding of the specific mechanisms behind epigenetic inheritance or exact effect size for the disease risk in offspring.

Pharmacological approaches have reached their limits..”

before presenting their belief that a hypothetical series of future CRISPR-Cas9 experiments will demonstrate the truth of their agenda.


The review focused on 0.0001% of the prenatal period for what matters with the human male – who he was at the time of a Saturday night drunken copulation – regarding intergenerational and transgenerational epigenetic inheritance of metabolic diseases.

The human female’s role – who she was at conception AND THEN what she does or doesn’t do during the remaining 99.9999% of the prenatal period to accommodate the fetus and prevent further adverse epigenetic effects from being intergenerationally and transgenerationally transmitted  – wasn’t discussed.

Who benefits from this agenda’s narrow focus?

If the review authors sincerely want to:

“Raise societal awareness of behavior to prevent a further rise in the prevalence of metabolic diseases in future generations..”

then EARN IT! Design and implement HUMAN studies to test what’s already known from epigenetic inheritance animal studies per Experience-induced transgenerational programming of neuronal structure and functions. Don’t disguise beliefs with the label of science.

http://jme.endocrinology-journals.org/content/early/2017/12/04/JME-17-0189.full.pdf “DNA methylation in epigenetic inheritance of metabolic diseases through the male germ line”

Beliefs about genetic and environmental influences in twin studies

This 2017 Penn State simulation found:

“By taking advantage of the natural variation in genetic relatedness among identical (monozygotic: MZ) and fraternal (dizygotic: DZ) twins, twin studies are able to estimate genetic and environmental contributions to complex human behaviors.

In the standard biometric model when MZ or DZ twin similarity differs from 1.00 or 0.50, respectively, the variance that should be attributed to genetic influences is instead attributed to nonshared environmental influences, thus deflating the estimates of genetic influences and inflating the estimates of nonshared environmental influences.

Although estimates of genetic and nonshared environmental influences from the standard biometric model were found to deviate from “true” values, the bias was usually smaller than 10% points indicating that the interpretations of findings from previous twin studies are mostly correct.”

The study model’s input was five phenotypes that varied the degrees of:

  1. Genetic and epigenetic heritability;
  2. Shared environmental factors; and
  3. Nonshared environmental factors.

Item 1 above was different than the standard model’s treatment of heritable factors, which considers only additive genetic influences.

The authors cited studies for moderate and significant shared environmental influences in child and adolescent psychopathology and parenting to support the model’s finding that overall, item 2 above wasn’t underestimated.


I wasn’t satisfied with the simulation’s description of item 1 above. With

  1. Environmental influences accounted for elsewhere, and
  2. No references to transgenerational epigenetic inheritance,
  3. Randomness seemed to be the only remaining explanation for an epigenetic heritability factor.

Inserting the model’s non-environmental randomness explanation for epigenetic heritability into the abstract’s statement above exposed the non sequitur:

In the standard biometric model when MZ or DZ twin similarity differs from 1.00 or 0.50, respectively, the variance that should be attributed to genetic [and non-environmental stochastic heritability] influences is instead attributed to nonshared environmental influences, thus deflating the estimates of genetic [and non-environmental stochastic heritability] influences and inflating the estimates of nonshared environmental influences.

Why did the researchers design their model with an adjustment for non-environmental epigenetic heritability? Maybe it had something to do with:

“Estimates of genetic and nonshared environmental influences from the standard biometric model were found to deviate from “true” values.”

In any event, I didn’t see that this simulation was much more than an attempt to reaffirm a belief that:

“The interpretations of findings from previous twin studies are mostly correct.”


Empirical rather than simulated findings in human twin study research are more compelling, such as The primary causes of individual differences in DNA methylation are environmental factors with its finding:

“Differential methylation is primarily non-genetic in origin, with non-shared environment accounting for most of the variance. These non-genetic effects are mainly tissue-specific.

The full scope of environmental variation remains underappreciated.”

https://link.springer.com/article/10.1007/s10519-017-9875-x “The Impact of Variation in Twin Relatedness on Estimates of Heritability and Environmental Influences” (not freely available)

Do preventive interventions for children of mentally ill parents work?

The fifth and final paper of Transgenerational epigenetic inheritance week was a 2017 German/Italian meta-analysis of psychiatric treatments involving human children:

“The transgenerational transmission of mental disorders is one of the most significant causes of psychiatric morbidity. Several risk factors for children of parents with mental illness (COPMI) have been identified in numerous studies and meta-analyses.

There is a dearth of high quality studies that effectively reduce the high risk of COPMI for the development of mental disorders.”


I found the study by searching a medical database on the “transgenerational” term. The authors fell into the trap of misusing “transgenerational” instead of “intergenerational” to describe individuals in different generations.

Per the definitions in A review of epigenetic transgenerational inheritance of reproductive disease and Transgenerational effects of early environmental insults on aging and disease, for the term “transgenerational transmission” to apply, the researchers needed to provide evidence in at least the next 2 male and/or 3 female generations of:

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

The meta-analysis didn’t provide evidence for “transgenerational transmission of mental disorders.”


Several aspects of the meta-analysis stood out:

  1. Infancy was the earliest period of included studies, and studies of treatments before the children were born were excluded;
  2. Parents had to be diagnosed with a mental illness for the study to be included;
  3. Studies with children diagnosed with a mental illness were excluded; and
  4. Studies comparing more than one type of intervention were excluded.

Fifty worldwide studies from 1983 through 2014 were selected for the meta-analysis.

Per item 1 above, if a researcher doesn’t look for something, it’s doubtful that they will find it. As shown in the preceding papers of Transgenerational epigenetic inheritance week, the preconception through prenatal periods are where the largest epigenetic effects on an individual are found. There are fewer opportunities for effective “preventive interventions” in later life compared with these early periods.

Science provides testable explanations and predictions. The overall goal of animal studies is to help humans.

Animal studies provide explanations and predictions for the consequences of environmental insults to the human fetus – predictable disrupted neurodevelopment with subsequent deviated behaviors and other lifelong damaging effects in the F1 children. The first four papers I curated during Transgenerational epigenetic inheritance week provided samples of which of these and/or other harmful effects may be predictably found in F2 grandchildren, F3 great-grandchildren, and future human generations.

When will human transgenerational epigenetic inheritance be taken seriously? Is the root problem that human societies don’t give humans in the fetal stage of life a constituency, or protection against mistreatment, or even protection against being arbitrarily killed?


The default answer to the meta-analysis title “Do preventive interventions for children of mentally ill parents work?” is No. As for the “dearth of high quality studies” complaint: when treatments aren’t effective, is the solution to do more of them?

No.

The researchers provided an example of the widespread belief that current treatments for “psychiatric morbidity” are on the right path, and that the usual treatments – only done more rigorously – will eventually provide unquestionable evidence that they are effective.

This belief is already hundreds of years old. How much longer will this unevidenced belief infect us?

http://journals.lww.com/co-psychiatry/Abstract/2017/07000/Do_preventive_interventions_for_children_of.9.aspx “Do preventive interventions for children of mentally ill parents work? Results of a systematic review and meta-analysis” (not freely available)