Network analysis of mitonuclear GWAS reveals functional networks and tissue expression profiles of disease-associated genesReport as inadecuate




Network analysis of mitonuclear GWAS reveals functional networks and tissue expression profiles of disease-associated genes - Download this document for free, or read online. Document in PDF available to download.

Human Genetics

, Volume 136, Issue 1, pp 55–65

First Online: 04 October 2016Received: 12 July 2016Accepted: 28 September 2016

Abstract

While mitochondria have been linked to many human diseases through genetic association and functional studies, the precise role of mitochondria in specific pathologies, such as cardiovascular, neurodegenerative, and metabolic diseases, is often unclear. Here, we take advantage of the catalog of human genome-wide associations, whole-genome tissue expression and expression quantitative trait loci datasets, and annotated mitochondrial proteome databases to examine the role of common genetic variation in mitonuclear genes in human disease. Through pathway-based analysis we identified distinct functional pathways and tissue expression profiles associated with each of the major human diseases. Among our most striking findings, we observe that mitonuclear genes associated with cancer are broadly expressed among human tissues and largely represent one functional process, intrinsic apoptosis, while mitonuclear genes associated with other diseases, such as neurodegenerative and metabolic diseases, show tissue-specific expression profiles and are associated with unique functional pathways. These results provide new insight into human diseases using unbiased genome-wide approaches.

Simon C. Johnson and Brenda Gonzalez contributed equally to this work.

Electronic supplementary materialThe online version of this article doi:10.1007-s00439-016-1736-9 contains supplementary material, which is available to authorized users.

Download fulltext PDF



Author: Simon C. Johnson - Brenda Gonzalez - Quanwei Zhang - Brandon Milholland - Zhengdong Zhang - Yousin Suh

Source: https://link.springer.com/







Related documents