Codon#2: What I was reading last week on genetics, omics & deep phenotyping

July 21-27

Below are some articles I found to be interesting reads on the topics of genetics, omics, and deep phenotyping last week.

1. Tissue-specific proteomic aging clocks

A mass spectrometry-based study of 13 tissues spanning 76 individuals aged 14 to 68 years developed tissue-specific proteomic aging clocks and showed earliest aging signs in arterial tissue.

🔗 https://www.cell.com/cell/abstract/S0092-8674(25)00749-4

2. A polygenic risk score for obesity shows high applicability potential

A PRS trained on a GWAS of 5.1 M individuals explained up to 17% in variance of BMI and showed meaningful contributions to predicting adult obesity in childhood, midlife obesity in young adults, and weight change in response to lifestyle interventions!

🔗 https://www.nature.com/articles/s41591-025-03827-z

👉 I also expanded on this article on a separate tweet.

3. A GWAS resource for physical activity

The largest to-date GWAS of physical acivity in up to up to 548,617 individuals of Europen, African & Latin American ancestry revealed 56 associated genomic loci.

🔗 https://www.nature.com/articles/s41588-025-02260-9

📊 summ stats: https://phenomics.va.ornl.gov/web/cipher/partner/mvp (email to CIPHER@va.gov with title "MVP and Meta-analyses Summary Results – Galimberti et al")

4. Plasma proteomics as endpoints in clinical trials

In a MASH trial, semaglutide showed dose-dependent effects on serum proteomic signatures of liver histology mirroring actual histolological outcomes. The study also developed a signature of semaglutide-induced MASH resolution.

🔗 https://www.nature.com/articles/s41591-025-03799-0

👉 This represents a very promising application of genomics in drug development that could help de-risk and prioritize candidates in phase 2 studies.

Enjoy the read!