Codon #1: This week's reads on genetics, omics & deep phenotyping
July 14-20 2025
Every week I’m sharing papers I found interesting in the fields of genetics, omics, and deep phenotyping.
This week’s reading list includes 7 articles:
The Global Neurodegeneration Proteomics Consortium
Described across 4 papers, a major effort harmonizing aptamer-based proteomics across 35,000 serum, plasma, and CSF samples from neurodegenerative disease-focused cohorts.
👉 A key step toward biomarker discovery and mechanistic insight into neurodegeneration. The effort shows the way for similar initiatives in other aging-related disorders.
🔗 Overview paper: https://www.nature.com/articles/s41591-025-03834-0#Abs1
🧵 My X thread summarizing all 4 papers: https://x.com/MariosGeorgakis/status/1946300675136295420
Rare structural genetic variation and psychiatric disease
Analyzing data for 6 major diagnostic psychiatric categories in 574,965 individuals, these two papers describe the discovery and biological pathways connected to rare copy number variants (CNV)—largely underresearched compared to SNPs— with psychiatric diagnoses.
👉 Rare CNVs accounted for 1-3% of heritability with some of them showing very large effects on disease liability.
🔗 https://www.medrxiv.org/content/10.1101/2025.07.11.25331310v2
🔗 https://www.medrxiv.org/content/10.1101/2025.07.11.25331381v2
The Human Phenotype Project
A description of the Human Phenotype Project (HPP), a growing dataset of >13,000 participants (already 28,000 have provided consent for enrollment) that aims at dynamic multi-modal deep phenotyping to better understand health & disease risk.
👉 The HPP aims at biennial assessment of study participants over 25 years offering the potential for dynamic serial multi-modal assessments over the lifetime.
🔗 https://www.nature.com/articles/s41591-025-03790-9
A proteomic biomarker for the diagnosis of pediatric tuberculosis
Addressing the poor performance of existing TB diagnostics in children, this study detects proteomic signatures of 3 to 6 proteins that achieve AUCs of 0.87-0.88, meeting the WHO accuracy threshold for a screening test.
🔗 https://www.nature.com/articles/s41467-025-61515-5
Vascular aging assessment in aortic MRI
An aging clock trained in geometric phenotypes from aortic MRI in UK and Penn Medicine Biobanks displayed associations with cardiovascular disease phenotypes and revealed genetic determinants of arterial aging.
🔗 https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.125.074554
A GWAS of clonal hematopoiesis (CHIP)
This GWAS of CHIP in 731,835 individuals implicates new germline risk loci and offers a useful resource for further downstream explorations.
🔗 https://www.nature.com/articles/s41588-025-02250-x
Genomic architecture of facial characteristics
This GWAS links genetic variation to 946 facial features obtained from 3D digital facial images of 11,662 individuals of European descent with replication in 9,674 Chinese. It detects 188 genomic loci associated with facial variation and improves prediction of the highly heritable facial features with implications for forensics.
👉 This is a well-conducted study, a cool application example of C-GWAS across multiple correlated traits, and a fun-to-read manuscript linking the findings to data from Neanderthals and other archaic humans!
🔗 https://www.nature.com/articles/s41467-025-61761-7
