Article

A candidate gene study of obstructive sleep apnea in European Americans and African Americans.

Division of Allergy, Pulmonary and Critical Care, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
American Journal of Respiratory and Critical Care Medicine (impact factor: 11.08). 10/2010; 182(7):947-53. DOI:10.1164/rccm.201002-0192OC pp.947-53
Source: PubMed

ABSTRACT Obstructive sleep apnea (OSA) is hypothesized to be influenced by genes within pathways involved with obesity, craniofacial development, inflammation, and ventilatory control.
We conducted the first candidate gene study of OSA using family data from European Americans and African Americans, selecting biologically plausible genes from within these pathways.
A total of 1,080 single nucleotide polymorphisms (SNPs) were genotyped in 729 African Americans and 505 SNPs were genotyped in 694 European Americans. Coding for SNPs additively, association testing on the apnea-hypopnea index (AHI) as a continuous trait, and OSA as a dichotomous trait (AHI ≥15) was conducted using methods that account for familial correlations in models adjusted for age, age-squared, and sex, with and without body mass index.
In European Americans, variants within C-reactive protein (CRP) and glial cell line-derived neurotrophic factor (GDNF) were associated with AHI (CRP: β = 4.6; SE = 1.1; P = 0.0000402) (GDNF: β = 4.3; SE = 1; P = 0.0000201) and with the dichotomous OSA trait (CRP: odds ratio = 2.4; 95% confidence interval, 1.5-3.9; P = 0.000170) (GDNF: odds ratio = 2; 95% confidence interval, 1.4-2.89; P = 0.0000433). In African Americans, rs9526240 within serotonin receptor 2a (HTR2A: odds ratio = 2.1; 95% confidence interval, 1.5-2.9; P = 0.00005233) was associated with OSA.
This candidate gene analysis identified the potential role of genes operating through intermediate disease pathways to influence sleep apnea phenotypes, providing a framework for focusing future replication studies.

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Keywords

1,080 single nucleotide polymorphisms
 
694 European Americans
 
apnea phenotypes
 
apnea-hypopnea index
 
association testing
 
biologically plausible genes
 
body mass index
 
candidate gene analysis
 
continuous trait
 
dichotomous OSA trait
 
European Americans
 
familial correlations
 
family data
 
first candidate gene study
 
future replication studies
 
glial cell line-derived neurotrophic factor
 
intermediate disease pathways
 
potential role
 
serotonin receptor 2a
 
ventilatory control