Pinned Tweet
Delighted to share our latest research from the @23andMeResearch Team, just published in @Nature
! We looked at data from >27,000 participants to uncover how human genetics influences weight loss efficacy and side effects of GLP-1 medications like semaglutide. A thread 🧵👇
14
66
237
60,670
What can we learn about a single rare variant?
Published today in Science: the @23andMeResearch Institute and Dana-Farber studied the EGFR T790M in 11M 23andMe research participants. The variant has OR = 25.2 for lung cancer, rising to 61.7 in never-smokers(!). 🧵
1
22
84
8,755
This paper is a beautiful example of what a large direct-to-consumer cohort makes possible: T790M is rare enough that its risk had never been reliably estimated. Its origins and distribution may support geographically targeted testing.
science.org/doi/10.1126/scie…
1
1
10
731
Huge congratulations to the incredible @23andMeResearch and Dana-Farber teams for getting this over the finish line. And *as always*, a massive thank you to the 23andMe participants who make this research possible!
5
593
Adam Auton retweeted
Discovery of a rare gene EGFR variant that predisposes to lung cancer, a 25-fold risk among carriers, a risk that exceeds smoking, high-risk seen in non-smokers, on the cover @ScienceMagazine, with trace of origin to a Southern Appalachia founder event
science.org/doi/10.1126/scie…
18
137
506
44,549
Adam Auton retweeted
As promised, I put together my thoughts on the ZEUS failure of IL-6 inhibition in atherosclerotic cardiovascular disease and what it means for drug development efforts centered around human genetics.
🔗Link: thecodon.substack.com/p/why-…
It looks like a brutally null result that doesn't leave much room for alternative interpretations. Given the strong genetic support (still holds), I didn't expect it.
Genetic variation in both the receptor and the ligand that downregulates the signaling cascade (as captured by CRP, fibrinogen etc) is associated with lower risk of all forms of ASCVD (AMI, CAD, stroke, PAD, carotid plaques). Variants in IL6R pop up in all GWASs for ASCVD phenotypes. Beyond genetics, IL-6 levels are associated with worse CVD outcomes in all epidemiological studies of primary or secondary prevention settings. And in CANTOS, the benefit of canakinumb was restricted to those, who achieved low IL-6 levels.
Still, it's an important reminder that no therapy works until we crash-test it in trials. Ofc the setting is important and Novo's choice to go for a CKD population, where mechanisms contributing to CVD are likely different, always felt somewhat weird to me. Signals for incident disease in genetic studies might not work well there. Still, if IL-6 signaling was crucial, I'd expect to see some effect.
Definitely, an opportunity to also reflect on the human genetics side of things in drug development. Genetics for sure points to relevant pathways, but clinical development is a different monster. The fact that a pathway is relevant for incident atherosclerosis doesn't mean that targeting it in patients with CKD, who are on aggressive lipid-lowering therapy and 7 other medications would lower MACE. There are interesting examples, where genetics and clinical development deviated, e.g. for factor XI (open.substack.com/pub/thecod…). People who now criticize genetics because "it doesn't always work" should check the <10% success rates of the industry overall.
I'll put my thoughts together and write something in the next days/weeks (or after the full results become available). I'd just like to note that very few therapeutic hypotheses have this level of converging support before they proceed to trials (animal studies, human genetics, epidemiology, even indirect trial evidence). So, I find the comments of everyone here, who "always expected the results" based on their gut feelings very interesting.
12
25
125
28,643
23andMe is hiring for 2 amazing roles!
- Scientist, ML for Health Risk Prediction: build next-gen health prediction tools integrating genetics.
- Scientist, Population Genetics: build state-of-the-art algorithms for genetic relationship & ancestry inference.
Links below!
1
10
44
32,448
ML for health prediction:
23andme.wd5.myworkdayjobs.co…
Population Genetics:
23andme.wd5.myworkdayjobs.co…
1
4
687
Adam Auton retweeted
We are devastated to learn of the passing of Kevin Keegan, one of the most iconic, influential and deeply loved figures in our club’s history.
Kevin was more than a legendary footballer and manager. He was the beating heart of Newcastle United for generations of supporters.
841
3,378
24,439
4,184,022
Adam Auton retweeted
It's mind blowing that people still don't understand basic experimental design. And what's worse is that some of the MLbio crowd genuinely believe that their models can magically get around confounds.
2
4
56
4,704
Adam Auton retweeted
Fascinating paper by @EadaoinSays and colleagues, with the help of @smithsonian, @harvardmed, @HarvardHEB, and @23andMeResearch, on the genetic legacy of @HistoricStMarys, the first capital of the Province of #Maryland. @StateMaryland @America250 cell.com/current-biology/ful…
1
211
Adam Auton retweeted
🧬A fascinating DNA study of Maryland’s first English colonial capital in the 17th century. Population-scale genetic data and fine-scale bioinformatics can literally restore names to people from the past.⛪
Scientists at @23andMeResearch analyzed DNA from 49 people who lived in St. Mary’s City around 350 to 390 years ago and identified more than 1.3 million modern genetic relatives. They traced links to western England, Wales, and Ireland and detected the genetic signature of a historical migration to Kentucky.
Most impressively, by comparing ancient DNA with living people’s family trees, the authors cautiously proposed identities for three burials, including Thomas Greene, the second governor of Maryland.
Genealogical questions at this time depth are usually approached through Y chromosome analysis. Here, however, the authors used IBD segments, matching stretches of DNA in the autosomes. This could open the door to much broader use of this method for reconstructing deep genealogies.
cell.com/current-biology/ful…
#Genealogy #aDNA #IBDSegments #PopulationGenetics #AncestryInference
2
11
89
6,051
Adam Auton retweeted
The second governor of colonial Maryland (and others) and relatives have been identified by the polytropos @EadaoinSays and team in a new paper that combines archaeology, anthropology, early US history, @23andMe participants, and the magic of ancient DNA.
I'm thrilled to share our new paper out today in @CurrentBiology! I teamed up with researchers at @harvardmed / @HarvardHEB and @smithsonian to study another historical American population using the @23andMeResearch genetic database. 🧵 [1/9]
Read it here: cell.com/current-biology/ful…
2
3
24
2,277
Adam Auton retweeted
Another awesome paper resulting from the Harvard/23&Me collaboration, led by @EadaoinSays! This work presents genomic data from 49 colonial settlers from
@HistoricStMarys, the founding settlement of Maryland!
I'm thrilled to share our new paper out today in @CurrentBiology! I teamed up with researchers at @harvardmed / @HarvardHEB and @smithsonian to study another historical American population using the @23andMeResearch genetic database. 🧵 [1/9]
Read it here: cell.com/current-biology/ful…
1
5
17
3,745
Adam Auton retweeted
Cool new paper by scientists from @23andme @smithsonian, and @harvard that combines genetic and genealogical info to propose identities for previously unknown individuals buried in St. Mary’s City cell.com/current-biology/ful…
3
4
2,720
This story is *really cool* - well worth a read. A great example of genealogical sleuthing with DNA. A huge congratulations to the amazing @23andMe team. (I wasn’t involved with this study)
I'm thrilled to share our new paper out today in @CurrentBiology! I teamed up with researchers at @harvardmed / @HarvardHEB and @smithsonian to study another historical American population using the @23andMeResearch genetic database. 🧵 [1/9]
Read it here: cell.com/current-biology/ful…
1
4
532