Fantastic work, really interesting to see MC4R extend its role beyond apptetite. We’ve also found surprisingly frequent POMC risk and MC4R protective variants in the Estonian population; We’ll check if retrospective semaglutide data from the Estonian Biobank align with the tirzepatide findings :)

Characterization of prevalent genetic variants in the Estonian Biobank body-mass index GWAS Nature Communications - Here the authors perform a genome wide association study of 204,747 Estonian Biobank participants revealing 214 BMI loci. Reported signals include ADGRL3, PTPRT, and a...

7/7 Take-home: even in well-studied European populations, there’s hidden biology waiting to be found. Using population-specific imputation panels lets you see uncommon and rare variants that global panels often miss.
rdcu.be/eJ0ge #GWAS #genetics #obesity @natcomms.nature.com

6/7 Also also: an intronic protective ADGRL3 variant, located near CTCF sites. ADGRL3 gene is better known for its role in neurodevelopment and ADHD and is for first time linked to BMI; it has intriguing possibly has ties to incretin biology (GIP). Worth a deeper functional look!

5/7 We also found a few noteworthy novel protective coding hits: PTPRT:p.Arg1384His associates with lower BMI and points to the leptin–melanocortin axis. As phosphatases are considered druggable, this could be a potential anti-obesity target to explore.

4/7 An almost identical variant has previously been found in labrador retrievers, which leads to increased food motivation and body weight (@stephenorahilly.bsky.social ). We can hypothesize that this variant leads to similar traits in humans as well.

3/7 Highlight: a stop-gain POMC variant (p.Glu206*) that truncates β-MSH & β-endorphin. And it's surprisingly common: >1,700 heterozygous carriers in Estonia (~0.85% of Estonian Biobank participants); likely tens of thousands across N/E Europe.

2/7 We used the youngest available adult BMI per person to amplify genetic signal (median age ~42, which is about 15–20 years younger than other similar biobank cohorts). Result: 214 genome-wide loci in EstBB, mostly neurological pathways, many known, plus some fresh ones.

1/7 New BMI GWAS out! Using Estonian Biobank (n=204,747) and replication in FinnGen, we show that even in Europe you can still find region-specific biology if you zoom into population-tailored sumstats. Big thanks to co-author @kanwalbatool.bsky.social :)

Ega jõua ka kõike kõikjal ja korraga :)

The Estonian Biobank’s journey from biobanking to personalized medicine - Nature Communications Large-scale biobanks have become a font of data that have led to discoveries across many fields of research. Here, the authors provide an overview of the Estonian Biobank, highlighting its value for r...

Excited to share our recently published overview of the @estbiobank.bsky.social 🧬
We highlight the unique features of the biobank and the conducted scientific research it has enabled, including the many recall studies that have been carried out over the years!
www.nature.com/articles/s41...