Eric Fauman (he/him)

This was the random page on the internet that set me down this rabbit hole:

www.tomsguide.com/wellness/fit...

DeGETTE: Will you commit that neither you or anyone else at HHS will take retaliatory action against the brave scientists at NIH? Should be an easy answer bc it's illegal

RFK Jr: I can commit that we are absolutely depoliticizing science at NIH for the first time


D: I asked you a simple question

It could be like designing an antibody to reduce circulating cystatin C levels in an attempt to improve kidney function...

And if that's the case, then we haven't really established a causal link between making people walk faster and seeing them age slower.

Investigation of a UK biobank cohort reveals causal associations of self-reported walking pace with telomere length - Communications Biology Mendelian randomisation analysis of the UK Biobank cohort, supported by analyses of accelerometer-measured activity intensity, reveals that genetically-determined walking pace is associated with longe...

This makes no sense to me.

How does genetically predicted walking speed relate to biological aging (here as telomere length( except as some sort of biomarker of overall health?

www.nature.com/articles/s42...

Exome sequencing and analysis of 44,028 British South Asians enriched for high autozygosity Genes and Health (G&H) is a biomedical study of adult British-Pakistani and -Bangladeshi research volunteers enriched for autozygosity. We performed whole exome sequencing in 44,028 G&H participants, ...

To add to your weekend reading, check out this nice report on the Genes & Health cohort from Hye In Kim, David van Heel and many many more:

www.medrxiv.org/content/10.1...

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Thanks for these caveats.
I guess I'm just surprised a major chromosomal rearrangement can fix in a population so quickly with no apparent impact on the effective population size. Is there good literature on this across other species.

(I did hedge a bit in my opening post calling it a "possible bottleneck")...

Pirruccello #eshg2025 - “There is really one game in town right now that is @ukb UKB.” - no one else is producing image data in healthy heart at this scale. @ukbiobank.bsky.social Taking a deep-dive into image-derived phenotypes such as sphericity and cardiac age acceleration.

This looks great. Reminds me to set aside time to read the whole thing.

Yes, I saw that paper but don't know enough to weigh the claims of either paper. Have you registered an opinion?

We do know chimps have 48 chromosomes and we have 46 so there must have been a first fusion carrier and that must have caused some reproductive difficulties.

Interestingly the original paper doesn't say the 99% went extinct, it says they were "lost" to our lineage, which is consistent with my model.

The quote: "98.7% of human ancestors were lost at the beginning of the bottleneck, thus threatening our ancestors with extinction".

Any population geneticist want to weigh in on whether any of this makes sense.

Last appearance of Homo erectus at Ngandong, Java, 117,000–108,000 years ago - Nature Bayesian modelling of radiometric age estimates provides a robust chronology for Homo erectus at Ngandong (Java), confirming that this site currently represents the last known occurrence of this speci...

In this model the larger population of unfused individuals persisted for up to 800k years.
There's a report of H erectus remains from only 100,000 years ago.

Whether we outcompeted our unfused cousins or it was just blind luck I think is not known.

www.nature.com/articles/s41...

In this model the effective population size reflects some kind of weighted sum of (reduced cross viability with the larger unfused population) and (higher reproductive success with the smaller fusion carriers).

In absolute terms I imagine there was a "bottleneck" of one chr2 fusion carrier.

All the non-fusion carriers are still around but we'd expect reduced reproductive success between fusion carriers and non-carriers.

No massive extinction event.

Just a genetic barrier between the original population and the fusion carriers.

Let's imagine a child was born 900kya with a chromosome 2 fusion. Chromosomal fusions occur today in 1:1000 live births.
Beating expectations this individual was able to reproduce, nucleating a small cohort of chr2 fusion carriers

molecularcytogenetics.biomedcentral.com/articles/10....

This figure and the coverage of the paper interpret the findings to mean that 99% of the human ancestors alive at the time were wiped out by some cataclysm like major climate change.

See here: www.nature.com/articles/d41...

But what if there was no extinction event, just reproductive isolation

This paper from late 2023 got a lot of attention in both the scientific and popular press based on the claim that the effective population size of humans was reduced to 1,280 individuals about 900k years ago

www.science.org/doi/10.1126/...

This is the authors' model:

I was today years old when I realized that the Chromosome 2 fusion event which is unique to modern humans probably coincides with a possible population bottleneck event ~900kya.

Could the one have caused the other?

This is my adaptation of the published figure

DOI: 10.1126/science.abq7487

In the comments section I saw someone else who got it in 3 and their first two guesses were:
CLEAR
RIGHT

which I thought was almost too perfect.

From Adam Butterworth: worth getting embroidered:

Happy Caturday!

These are Mage and Moxie, brothers to my avatar cat, Mojo.

How do you mean? They do a good job of keeping up with published GWAS.
And then open targets calculates credible sets for all the full summary statistics in the catalog.

Yes, Mojo, the all black cat, is my mews and inspiration.

He's patiently waiting for the first pet association wide study, aka PAWS.

Also, I'll be at Hinxton from April 28 to May 1st.

Love to catch up with anyone who might be around then.

We’re in U.S. District Court in Burlington, Vermont for Rümeysa Öztürk’s hearing. Today, the legal team is asking the judge to release her from detention.

Ideas aren’t illegal. Rümeysa must be released.

But do you put two spaces after a period. I hear we're not supposed to do that anymore.

It is now 2025.
There are 10s of thousands of gwas.

I hope @opentargets and similar tools will make it easier for everyone to consider the full complement of phenotypes caused by the genetic variant of interest.

In my experience this makes it far easier to infer the likely causal gene.