
Genetic variant accelerates normal brain aging in older people by up to 12 years - baalcat
http://neurosciencenews.com/genetics-brain-aging-6250
======
csl
Note: The following is _complete_ speculation and probably _bullshit_. Please
correct me!

I can't find the actual paper for this one. But reading _an older_ study [0],
also about TMEM106B, it seems they had already established an association
between three SNPs and frontotemporal lobar degeneration (FTLD) risk.

However, the surprise discovery back then seemed to be the large discrepancy
between the controls and the subgroup FTLD-GNR (those with FTLD and GNR
mutations) for TT rs6966915 and CC rs1990622. See table 2 in [0], and look at
the odds ratios. They are remarkably low for TT/CC, which invites further
study that may lead to understand how to protect against FTLD (by
understanding possible protective mechanisms, even therapies and so on).

As for listing out those odds ratios for your 23andMe genome, you can do it
with arv [1]. For table 1 in the study (unless you know you have GNR
mutations):

    
    
      import arv
      
      genome = arv.load("genome.txt")
      
      rsid = "rs6966915"
      gt = genome.get_snp(rsid).genotype # plus orientation
      print("%s %s" % (rsid, arv.unphased_match(gt, {
          "CC": "CC - OR 0.94",
          "CT": "CT - OR 1.04",
          "TT": "TT - OR 0.74"})))
      
      rsid = "rs1990622"
      gt = ~genome.get_snp(rsid).genotype # minus orientation
      print("%s %s" % (rsid, arv.unphased_match(gt, {
          "TT": "TT - OR 0.93",
          "CT": "CT - OR 1.04",
          "CC": "CC - OR 0.74"})))
    

Again, did I say that I'm a complete noob? Be very careful drawing conclusions
from the program (or believing I know what I'm talking about --- I don't!)

[0]:
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3034409/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3034409/)

[1]: [https://github.com/cslarsen/arv](https://github.com/cslarsen/arv)

~~~
said
I wonder whether this variant is similar to APOE E4 allele—which significantly
increases one's risk of Alzheimer's—in that its affect can be minimized by
lifestyle changes.

In men, APOE E4's disadvantages can be almost completely eliminated (compared
to APOE E3) by regularly exercising and completely abstaining from alcohol.

~~~
telarson
I haven't seen many research papers that claim abstaining from alcohol helps
reduce ALZ risk in E4 carriers. Care to share?

------
calebm
Looks like the main SNP in consideration is:
[https://www.snpedia.com/index.php/Rs1990622](https://www.snpedia.com/index.php/Rs1990622).
Anyone see the particular allele value that increases risk? My guess (looking
at some genetic family data) is if you having an "A" instead of a "G" is the
mutation - can anyone confirm?

~~~
calebm
Looks like that's it: "We identified 2 coding variants: one rare variant which
was observed in a single control (c.401G>A; p.S134N) and one common variant
(rs3173615, pT185S)."
([https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3034409/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3034409/))

~~~
calebm
Heads-up: 23andme data contains this gene:

cmbpr:raw_23andme caleb$ grep rs1990622 *.txt

genome_Person1.txt:rs1990622 7 12283787 GG

genome_Person2.txt:rs1990622 7 12283787 GG

genome_Person3.txt:rs1990622 7 12283787 AG

~~~
grandalf
I hope someone who understands the article can offer an explanation about
whether it's possible to use the 23andme data to speculate about one's own
susceptibility to this.

~~~
09bjb
Seconded.

------
hueving
As I've gotten older I've noticed my memory is not as good (both short term -
what was I talking about, and long term - what was the very obvious term for
this thing I've said many times in the past).

Any other middle-aged people (early 40s) experience this? What degree of it is
just "your brain sucks as you age"?

~~~
startupdiscuss
I have found that times in my life when I exercised less, I forgot more.

I also find less time to exercise as I grow older.

However, for the same level of exercise, rest, and study, I can't tell if
there is a difference.

I also have more to forget, so I can barely remember entire arguments in
philosophy that I had down cold 10 years ago, but even at age 20, you may not
remember much from when you were 10.

~~~
bootload
_" I have found that times in my life when I exercised less, I forgot more. I
also find less time to exercise as I grow older."_

Want to improve your memory and brain function at any age? Exercise. [0] Want
to add new neurons (neurogenesis), exercise. [1] Want to improve your neuro-
plasticity? [2] Learn new skills.

It's always bothered me nerds/tech-heads optimise their lifestyles for time,
not realising fitness, novelty and rest can be used as a strategic weapon to
getting better at what you do. I'm not being critical of the OP, I'm just
observing what I see in my own tech circles.

Reference

[0] [http://www.health.harvard.edu/blog/regular-exercise-
changes-...](http://www.health.harvard.edu/blog/regular-exercise-changes-
brain-improve-memory-thinking-skills-201404097110)

[1] [https://www.dnalc.org/view/848-Exercise-induced-
Neurogenesis...](https://www.dnalc.org/view/848-Exercise-induced-
Neurogenesis.html)

[2]
[http://www.nature.com/nature/journal/v427/n6972/full/427311a...](http://www.nature.com/nature/journal/v427/n6972/full/427311a.html)

------
lngnmn
> “TMEM106B begins to exert its effect once people reach age 65,”

Genes does not work that way. Unless a specific protein and particular pathway
are identified, and the effect of mutated protein is validated, this is mere a
speculation.

~~~
ajross
That's only colloquial, not wrong. The corrolation between this gene and the
observed effects exists only after age 65. I don't see that this precision
would change much in the way the intended reader is going to interpret it.
Something about the presence of this gene[1] is causing early frontal cortex
degeneration after age 65.

[1] Unlike lots of other situations in medicine, the direction of causality is
known here: this gene obviously can't be the result of some other age-related
driver of degeneration. Genes do not work that way, heh.

------
throwaway2048
Cant wait till insurance drops people based on this gene

~~~
ajross
I know it's a joke, but it's important to point out for those who don't know
that the ACA as it stands right now disallows discrimination on the basis of
any pre-existing condition (which obviously includes genetic makeup), and even
the AHCA disaster currently failing to pass in the house doesn't change that.

The dystopia might arrive someday, but not now, and not in the near future.
Democrats (yes, it was all democrats) got it done seven years ago.

~~~
grandalf
> The dystopia might arrive someday, but not now, and not in the near future.
> Democrats (yes, it was all democrats) got it done seven years ago.

Fortunately most people (or someone they care about) are likely enough to
suffer from a genetically-linked, costly health issue that it seems unlikely
that discrimination would find much support.

~~~
thebooktocome
Strange, then, that the Republican-dominated House just passed a bill
weakening protections against discrimination on the basis of genetic
information.

[https://www.theatlantic.com/health/archive/2017/03/genetic-d...](https://www.theatlantic.com/health/archive/2017/03/genetic-
discrimination-law-gina/519216/)

~~~
grandalf
I think this is just due to a misunderstanding of how genetic traits and risks
work. Insurance companies may be angling for the government to be the insurer
of last resort for the most costly genotypes.

If there is anything that it makes sense to utilize a risk pool for, it is the
random chance associated with heredity. Aside from a small number of well
known, highly hereditary genetically-linked conditions, most people just
reproduce without thinking much about the probability that their offspring
will end up with an unlucky genotype. This is mainly because there is so much
chance involved and a low probability of the child getting a "costly" genome,
at least the cost impact of drawing a 99% probability genome is far less than
the impact of an additional year of maternal age, etc. Even for the most
strongly hereditary diseases, random chance still dominates the impact of
heredity on the chance of the offspring getting the disease.

Also, evolution ensures that most "harmful" genes are also helpful in some
way... so while there is likely an expected dollar cost of a given allele, I
don't think there's enough variation in overall dollar cost to make it worth
the hassle for anyone (including insurers), which points again to the notion
that they are simply looking for corporate welfare.

For comparison, post 9/11 the insurance industry extracted a big handout when
the US Government became the insurer of last resort for terrorism related
claims > $1B. My take is that genomes that are highly likely to cost more than
a standard deviation greater than average are rare enough that it wouldn't
even make sense from a competitive perspective for insurance companies to try
to evade issuing policies to such people.

------
kirykl
Could CRISPR be used to fix this?

~~~
kornork
Exactly what I was thinking... but when will you (and society) be comfortable
with a therapy that goes into your brain cells and edits their DNA?

~~~
coldtea
> _but when will you (and society) be comfortable with a therapy that goes
> into your brain cells and edits their DNA?_

Seconds after some early adopters have shown that it works and has no side-
effects?

~~~
maxerickson
No on will disagree with that answer.

Lots of people will argue vehemently about what it takes to be certain that
there are no side effects.

~~~
coldtea
Note that I didn't say: "Seconds after some early adopters tried it", but
"Seconds after some early adopters have shown that it works and has no side-
effects".

Which could be a few decades after some early adopters tried it -- e.g. until
they died in their 80s or 90s with perfect brain function...

So, seconds after that...

~~~
maxerickson
Right, that was my understanding.

I suppose my point was that kornork seemed to me to be talking about safety
and in that context, saying you'd do it after it is shown to be safe isn't
saying a lot.

~~~
coldtea
Aha, I took the parent's comments to be about the ethical and/or existential
questions.

After all we do various kinds of brain altering operations and take brain
altering drugs. DNA is not our personality, just how our body is built.

------
mrfusion
Would anyone be kind enough to post instructions for finding this in your
23andme data?

