Obstructive Sleep Apnea and Dementia-Common Gene Associations through Network-Based Identification of Common Driver Genes

Abstract

Background: Obstructive Sleep Apnea (OSA) occurs in 7% of the adult population. The relationship between neurodegenerative diseases such as dementia and sleep disorders have long attracted clinical attention; however, no comprehensive data exists elucidating common gene expression between the two diseases. The objective of this study was to (1) demonstrate the practicability and feasibility of utilizing a systems biology approach called network-based identification of common driver genes (NICD) to identify common genomic features between two associated diseases and (2) utilize this approach to identify genes associated with both OSA and dementia. Methods: This study utilized 2 public databases (PCNet, DisGeNET) and a permutation assay in order to identify common genes between two co-morbid but mutually exclusive diseases. These genes were then linked to their mechanistic pathways through Enrichr, producing a list of genes that were common between the two different diseases. Results: 42 common genes were identified between OSA and dementia which were primarily linked to the G-coupled protein receptor (GPCR) and olfactory pathways. No single nucleotide polymorphisms (SNPs) were identified. Conclusions: This study demonstrates the viability of using publicly available databases and permutation assays along with canonical pathway linkage to identify common gene drivers as potential mechanistic targets for comorbid diseases.

A Method for Bridging Population-Specific Genotypes to Detect Gene Modules Associated with Alzheimer’s Disease

“…In order to apply our pipeline to AD, we used 13 brain tissues reported to be associated with AD (Methods). Twenty-four of the gene modules discovered in the Hisp population are shared with the White population and 13 with the Afr population ( Table 2 ) [ 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ].…”

“…Only one module, including three genes C4orf27 (HPF1), KCNJ6 and TMEM218, is shared between the White and Afr populations and is also included in the 24 and 13 modules shared between Hisp, White and Afr populations, all identified in the brain cerebral hemisphere (another module that includes these three genes + IFNGR2 is shared between the Hisp and Afr populations). Interestingly, TMEM218 was identified as a common gene between obstructive sleep apnea and AD [ 36 ]. While KCNJ6 has no known direct association with AD, KNJC6 is associated with Down’s syndrome [ 37 , 38 ], which has a well-established increased risk for AD [ 39 ].…”

“…In order to apply our pipeline to AD, we used 13 brain tissues reported to be associated with AD (Methods). Twenty-four of the gene modules discovered in the Hisp population are shared with the White population and 13 with the Afr population (Table 2) [36][37][38][39][40][41][42][43][44][45][46]. In order to apply our pipeline to AD, we used 13 brain tissues reported to be associated with AD (Methods).…”