| Title: | Mapping the proteo-genomic convergence of human diseases |
| Journal: | Science |
| Published: | 12 Nov 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/34648354/ |
| DOI: | https://doi.org/10.1126/science.abj1541 |
| URL: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9904207 |
| Citations: | 247 (185 in last 2 years) as of 8 Aug 2024 |
Publication 12661
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Abstract
Characterization of the genetic regulation of proteins is essential for understanding disease etiology and developing therapies. We identified 10,674 genetic associations for 3892 plasma proteins to create a cis-anchored gene-protein-disease map of 1859 connections that highlights strong cross-disease biological convergence. This proteo-genomic map provides a framework to connect etiologically related diseases, to provide biological context for new or emerging disorders, and to integrate different biological domains to establish mechanisms for known gene-disease links. Our results identify proteo-genomic connections within and between diseases and establish the value of cis-protein variants for annotation of likely causal disease genes at loci identified in genome-wide association studies, thereby addressing a major barrier to experimental validation and clinical translation of genetic discoveries.</p>
22 Keywords
- Aging
- Alternative Splicing
- Blood Proteins
- COVID-19
- Connective Tissue Diseases
- Disease
- Drug Development
- Female
- Gallstones
- Genetic Association Studies
- Genetic Variation
- Genome, Human
- Genome-Wide Association Study
- Genomics
- Humans
- Internet
- Male
- Phenotype
- Proteins
- Proteome
- Quantitative Trait Loci
- Sex Characteristics
21 Authors
- Maik Pietzner
- Eleanor Wheeler
- Julia Carrasco-Zanini
- Adrian Cortes
- Mine Koprulu
- Maria A Wörheide
- Erin Oerton
- James Cook
- Isobel D Stewart
- Nicola D Kerrison
- Jian'an Luan
- Johannes Raffler
- Matthias Arnold
- Wiebke Arlt
- Stephen O'Rahilly
- Gabi Kastenmüller
- Eric R Gamazon
- Aroon D Hingorani
- Robert A Scott
- Nicholas J Wareham
- Claudia Langenberg
Enabling scientific discoveries that improve human health