The growing evidence showed that the OSA is a heritable complex genetic disease where the genetic basis contributed the development of OSA and its sequel. The phenotyping of OSA include high level and intermediate level. The former indicates the AHI, and later includes craniofacial morphology, ventilator control, obesity, and sleepiness vulnerability. Many studies tried to determine the association of candidate genes with OSA through association studies. However, the results were conflicting. We identified 37 candidate genes involved in six biologic pathways of OSA reported in previous literatures, including oxidative phosphorylation, cell signaling, apoptosis, cellular adhesion and motility, cell cycle, and cytokine/chemokine. To investigate the association between phenotype and genotype of OSA, we conducted this cross-sectional study by recruiting the patients of moderate-severe OSA (index proband) and their first and second-degree family members, and friends and their family members (control family) and using candidate genes reported in the literature and whole genome SNP array for genotype approach.
Description: Phenotypes assessment by PSG, craniofacial image, Hypercapnic ventilatory response testing, psychomotor vigilance task, MSLT, blood biochemistry testing, abdominal MRI, and 24 hr ambulatory BP monitor Family aggregation assessed by family-based study design (1. to compare risk of OSA between index and control proband; 2. to compare risk between index proband with more than one families suffering OSA and without; 3. to calculate inter-generation and intra-generation association index of AHI)Measure: Family aggregation of OSA and its phenotype Time: within the first half year after enrollment
Description: Genotypes assessed by candidate genes identification or whole genome SNP array Phenotypes assessment by PSG, craniofacial image, Hypercapnic ventilatory response testing, psychomotor vigilance task, MSLT, blood biochemistry testing, abdominal MRI, and 24 hr ambulatory BP monitor Association assessed by linkage study and association studyMeasure: Association between phenotype and genotype of OSA Time: within the first half year after enrollment
There is one SNP
Also, the whole genome SNP array identified candidate genes associated with OSA as C-reactive protein (C-RP) and glial cell line-derived neurotrophic factor (GDNF) in European Americans and rs9526240 within serotonin receptor 2a (HTR2A) in African Americans.