[HN Gopher] Sperm DNA methylation epimutation biomarker for pate...
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Sperm DNA methylation epimutation biomarker for paternal offspring
autism
Author : johntfella
Score : 50 points
Date : 2021-06-11 06:49 UTC (16 hours ago)
(HTM) web link (doi.org)
(TXT) w3m dump (doi.org)
| johntfella wrote:
| Full title: Sperm DNA methylation epimutation biomarker for
| paternal offspring autism susceptibility
| TeeMassive wrote:
| > Methods and results
|
| > Sperm samples were obtained from fathers that have children
| with or without autism, and the sperm then assessed for
| alterations in DNA methylation. A genome-wide analysis (> 90%)
| for differential DNA methylation regions (DMRs) was used to
| identify DMRs in the sperm of fathers (n = 13) with autistic
| children in comparison with those (n = 13) without ASD children.
| The 805 DMR genomic features such as chromosomal location, CpG
| density and length of the DMRs were characterized. Genes
| associated with the DMRs were identified and found to be linked
| to previously known ASD genes, as well as other neurobiology-
| related genes. The potential sperm DMR biomarkers/diagnostic was
| validated with blinded test sets (n = 8-10) of individuals with
| an approximately 90% accuracy.
|
| This has to be a preliminary study right? I mean n=13...
| seanhandley wrote:
| > Autism spectrum disorder (ASD) has increased over tenfold over
| the past several decades
|
| That should be "Diagnosis of ASD has increased tenfold..."
| because of a heap of factors including the medical criteria of
| diagnosis changing, a historical underdiagnosis of autism in
| girls and women, and improved public knowledge of the condition
| leading to more assessments and diagnoses.
|
| EDIT:
|
| Towards the end, it says
|
| > The frequency of autism in the population has dramatically
| increased over tenfold the past several decades. This increase
| appears to be due in part to increased diagnosis efficiency from
| 1975 to the early 2000s, as well as greater public awareness of
| the disease [3]. The more recent increase in the last couple of
| decades suggests environmental factors, and exposures also have a
| critical role in autism prevalence.
| ghostpepper wrote:
| So are you saying our ability to detect it has not actually
| improved in the past several decades?
| seanhandley wrote:
| I'm saying an increase in diagnoses recently is in large part
| due to a historical underdiagnosis rather than an increasing
| frequency of children born with ASD. However, the paper hints
| at environmental factors being responsible for a proportion
| of the increase (but does not cite evidence to prove it).
| brutus1213 wrote:
| Paper seems to refer to environment factors and paternal
| DNA. Is this established or just a hypothesis (the paternal
| part especially)?
|
| It is kind of sad given the advances in sequencing and
| state of computing power that we cannot reliably diagnose
| this stuff with sequencing. I thought the promise of
| 23andme, and ilk was to gain large amounts of data and make
| progress on these problems (NIPT seems like a success
| though).
| h0l0cube wrote:
| For some this opinion might be contentious/taboo, but mild autism
| is prevalent across much of the skilled labor pool in STEM - and
| I count myself within that statistic. So it'll be interesting in
| a couple of generations what might happen to this labor pool if
| the potential to screen for the broad autism phenotype affects
| who is born and/or affects sexual selection.
| bozzcl wrote:
| Is it contentious? I thought it was pretty accepted. Pretty
| obvious too, even just looking at the people I know.
| mywittyname wrote:
| It hasn't really been studied or formalized in any way (at
| least that I know of). But I'm confident that it will be
| found to be the case if/when it is studied.
| renewiltord wrote:
| Since most STEM workers have fairly successful professional and
| personal lives and whatever behaviours you associate with
| Autism Spectrum Disorder don't lead to any harm in their lives,
| it's hard to accept that what they have is a 'disorder' in any
| sense any more than working hard is mild workaholism.
|
| If you have some cluster of traits that don't hurt you, then
| imho they're just traits, not a disorder.
| gopalv wrote:
| > If you have some cluster of traits that don't hurt you,
| then imho they're just traits, not a disorder
|
| Even more relevant is that some things could be cliff
| disorders, where it is actually beneficial till it actually
| falls over some point.
|
| Like Icarus flying, but takes him too close to the sun.
|
| Being obsessive about details making things or being paranoid
| about what you eat are probably great things to start with,
| but overrides its own utility at some point.
| TheSpiceIsLife wrote:
| This is such a good point.
|
| For example, there's _fastidious_ , which is a great to
| have in at least some members of a team, or to be able to
| draw on as a skill or trait for oneself; and then there's
| the same taken to an extreme which manifests as disorders
| such as OCD, hoarding, etc.
| [deleted]
| kokanator wrote:
| These traits are typically in clusters. You may have an
| amazing brain trait that accelerates your success and also
| have a sensory processing disorder which creates great
| discomfort.
|
| The cliff question would seem to be a very personal
| question. Where does that cliff exist? What traits create a
| cliff? ( not really looking for answer )
|
| I have two autists in my house. For them autism has created
| some substantial struggles when dealing with the world in
| general. However, their ( what I call super powers ) have
| allowed them great success in their given fields ( cs and
| research ).
|
| Both see the world substantially different than their mom
| and I do. Their view is often, simple and more forgiving.
|
| Autists have and continue to make great contributions to
| the neural typical world. My hope is that we are not on a
| road to eliminate these individuals from our world.[0]
|
| [0]https://www.appliedbehavioranalysisprograms.com/historys
| -30-...
| ivan888 wrote:
| > whatever behaviours you associate with Autism Spectrum
| Disorder don't lead to any harm in their lives
|
| It doesn't appear that the op made this claim.
|
| I think I understand your perspective. I think there are some
| ASD associated traits which may result in sort of a tradeoff
| for some STEM workers. E.g someone who has a difficulty
| forming interpersonal relationships (negative) may thus have
| more free time to pursue academics and outperform their more
| social peers (positive). This seems more like what the op was
| talking about being able to observe.
| skissane wrote:
| Some people have broad autism phenotype (BAP), which means
| they have many of the traits of ASD, but those traits are not
| sufficiently disabling to justify the label of a disorder.
| And BAP is more common among STEM workers than the general
| population.
|
| However, the boundary between BAP and ASD is not fixed.
| Different clinicians draw the line at different places, and
| it is moving over time. And which side of the line one ends
| up on can be determined by external life experiences. A
| person with BAP who lives a life full of luck and supportive
| environments may never be disabled by their traits to the
| extent that an ASD diagnosis is warranted. Give the same
| person worse luck and a more adverse environment, and the
| same traits may become much more disabling, and they may end
| up with an ASD diagnosis as a result. So, fundamentally the
| same person, whether they had ASD was determined not by who
| they are but by what their environment is.
|
| This is part of what annoys me about some of these popular
| lines that "autistic people" and "neurotypical people" are
| "wired differently". Are people with BAP "neurotypical" or
| not? And sometimes the label is determined, not by one's
| "wiring", but by stuff going on in the world outside one's
| head, by society and culture and family and friends and fate
| and fortune.
| bawolff wrote:
| Do STEM workers have succesful personal lives relative to
| people in other fields?
|
| I have no idea, but there are some sterotypes that they are
| below average. Would be interesting to see studies on that.
| renewiltord wrote:
| Personal lives are complex things, certainly, and no single
| metric can capture 'success' or 'failure' on them. However,
| one piece of evidence is the per-occupation divorce rate:
| https://flowingdata.com/2017/07/25/divorce-and-occupation
|
| Software folks are _really_ good about not getting
| divorced. And they have money, so they _could_ if they
| wanted to.
| dnautics wrote:
| My guess is that a large part of it is social. In STEM you
| don't have to be as personable to succeed. I'm perfectly
| capable of bringing a face, but even though I'm an
| extrovert god damn is it exhausting. Thankfully, working in
| stem I don't have to, so I don't, and I save my energy for
| non-work socialization.
| bawolff wrote:
| If you find it exhausting you're probably not an
| extrovert (extrovert/introvert is just about how much
| energy social stuff takes you, it has nothing to do with
| how much you socialize, how good you are at it, or how
| much you like it)
| dnautics wrote:
| I mean what I said: I find it exhausting to bring a face.
| When I'm interacting with people in a more organic
| setting I _gain energy_. -- definitely an extrovert. My
| primary non-work activity is highly social (social
| dance).
| ggggtez wrote:
| STEM make more money, and more money is associated with
| happiness.
|
| But you probably wanted something more conclusive.
| dragonwriter wrote:
| X correlates with Y & Y correlates with Z doesn't imply X
| correlates with Z.
| bawolff wrote:
| Also money generally doesn't correlate with happiness
| past a certain very basic point.
| wait_a_minute wrote:
| Give me some so I can test that theory ;)
| 1-6 wrote:
| You say statistic. Is there a document regarding this?
| skissane wrote:
| https://journals.plos.org/plosone/article?id=10.1371/journal.
| ..
|
| Autism Quotient (AQ) scores are generally accepted as a
| measure of Broad Autism Phenotype (BAP), which is subclinical
| ASD. That study produces the (entirely expected) conclusion
| that BAP is more common in men than women, and more common in
| STEM occupations than non-STEM occupations.
|
| I'm not aware of any studies linking software engineering
| specifically to BAP, as opposed to STEM occupations in
| general. I think the evidence on that point is (thus far)
| based on anecdote and clinical experience.
| seanhandley wrote:
| Also, ASD is massively underdiagnosed in girls and women
| for various reasons to do with societal expectations and a
| generally accepted better ability to mask autistic traits.
| skissane wrote:
| It may be true that ASD is under-diagnosed in girls and
| women [0]; but if it is, I'm not sure what relevance it
| has to this study, given this study was measuring self-
| report of the traits themselves, not whether one has a
| diagnosis. As a general population sample, it would
| include some people with a formal diagnosis, but the vast
| majority of people would lack one.
|
| [0] I'm sceptical about all claims around "overdiagnosis"
| and "underdiagnosis" because there is no objective answer
| as to where to draw clinical cutoffs, and the answer in
| practice is often driven by cultural factors. I think the
| gender distribution observed in diagnosis is partially
| innate (due to biological differences between the sexes)
| and partially a product of cultural influences. If one
| reads the claim that "underdiagnosed in girls and women"
| as talking about the role of those cultural influences, I
| agree with it. But I'm just not sure if "underdiagnosed"
| is the best way to put that claim.
| dvfjsdhgfv wrote:
| Does anyone know of a similar study but involving mothers instead
| of fathers?
| nightfly wrote:
| It's a lot more destructive to harvest eggs than sperm.
| aminozuur wrote:
| Fertility clinics harvest eggs from women every day. Some of
| those eggs could be donated for research.
|
| Example: Clinics harvests 12 eggs from a layd, 1 egg needed
| for IVF, IVF is succesful (baby born), lady is now happy to
| donate the remaining 11 eggs to science.
| fallingfrog wrote:
| "One of the control samples, IVI 14, had a very high sperm count
| of 396.62 million that was outside two standard deviations of the
| mean (2 +- SD), so the analysis was redone without this sample."
|
| Yeah having chuck norris in your study is going to skew any set
| of results.
| pvaldes wrote:
| Trying to reconstruct the title
|
| Found a mutation in spermatozoa that can be used as a flag for
| higher probability of having autistic children. Correct?
| Accujack wrote:
| More like "Found: an epigenetic change in sperm that seems to
| correlate with genes we know are involved in autism".
| tomp wrote:
| Methilation isn't a mutation. It's epigenetics - (potentially)
| persistent / heritable changes in phenotype (expressed genes)
| _outside_ of genetic code (DNA).
|
| It's used for many things, e.g. turning on/off specific genes
| in somatic cells, repairing DNA (when DNA is copied, the old
| strand is methilated; so you know how to fix any differences
| between old and new strand), and more recently, for measuring
| aging (Horvath epigenetic clock).
| skissane wrote:
| Two samples each with n = 13.
|
| ASD is widely acknowledged to be a highly heterogeneous condition
| which is likely to have multiple independent causes, and which
| has unclear boundaries with other diagnoses (especially ADHD)
|
| So a study which effectively treats ASD as a single
| undifferentiated condition, and has rather small sample sizes
| too, I think should be treated with a great deal of scepticism.
| nicoburns wrote:
| I agree with heterogeneous. But why do you think that auggests
| multiple causes. Commonalities across the neurodivergent
| spectrum intuitively lead me to suspect the opposite, that
| there is some common mechanism underlying all of them.
| skissane wrote:
| Because the same symptoms can be produced by widely different
| brain structures.
|
| Have you read this paper:
| https://www.nature.com/articles/s41398-019-0631-2
|
| They find that the four-way distinction between ASD, ADHD,
| OCD and "typically developing" has poor correspondence to the
| observed interaction between cortical morphology and
| behavioural symptoms.
|
| If you take their clusters -
| https://www.nature.com/articles/s41398-019-0631-2/figures/3 -
| as "what is really going on in the brain", then the same
| "what is really going on in the brain" can produce all four
| of ASD, ADHD, OCD and typical development, at different
| proportions (clusters 1-5). Whereas, conversely, there is a
| subgroup of ASD (cluster 10) which doesn't overlap with ADHD
| or OCD or typicality.
|
| I'd also recommend reading
| https://link.springer.com/article/10.1007/s40489-016-0085-x
| 2T1Qka0rEiPr wrote:
| Yes, I read down to this point and stopped. What significance
| can you really draw from a sample size of 26? (Serious question
| to academics out there)
| renewiltord wrote:
| To answer your serious question, n=26 is more than sufficient
| depending on effect size and sampling method.
|
| Think about it, if you have 26 people randomly sampled and
| you give half a pill and the other half a placebo and the
| first half dies moments after ingestion, how confident are
| you that the pill is poisonous?
|
| If the effect size is small, you may fail to detect it with a
| small population. If the sampling is biased, then you're
| going to have a problem even if you have a massive population
| studied.
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