Exploring the genetic blueprint of cerebrospinal fluid proteins, this study uncovers new markers and therapeutic targets that may unlock advancements in Alzheimer’s diagnosis and care. Study: Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and implicates causal proteins for Alzheimer’s disease . Image Credit: Kateryna Kon / Shutterstock In a recent study published in Nature Genetics , researchers investigated the genomic signature of the human cerebrospinal fluid (CSF) proteome.
Genome-wide association studies (GWASs) have become common over the past 15 years, with thousands of people studying many diseases and traits, revealing disease-associated loci. Nonetheless, translating associations to pathways and therapies is challenging, as identifying causal genes and their interactions requires integrating omics data and further downstream analyses. Analyses of the genetic regulation of gene expression have described loci affecting mRNA levels; however, such analyses miss disease-relevant biology.
Besides, the correlation between mRNA levels and their encoded proteins is weak, and therefore, the overlap between expression quantitative trait loci (eQTLs) and protein QTLs (pQTLs) is also low. Studies investigating genetic associations of proteins have predominantly focused on plasma, and reports suggest little overlap between plasma and brain proteogenomics. However, targeting CSF proteins has successfully elucidated causal gene.