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

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: ? = 4.6; SE = 1.1; P = 0.0000402) (GDNF: ? = 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.

SUBMITTER: Larkin EK

PROVIDER: S-EPMC2970865 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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

Larkin Emma K EK Patel Sanjay R SR Goodloe Robert J RJ Li Yali Y Zhu Xiaofeng X Gray-McGuire Courtney C Adams Mark D MD Redline Susan S

American journal of respiratory and critical care medicine 20100610 7

<h4>Rationale</h4>Obstructive sleep apnea (OSA) is hypothesized to be influenced by genes within pathways involved with obesity, craniofacial development, inflammation, and ventilatory control.<h4>Objectives</h4>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.<h4>Methods</h4>A total of 1,080 single nucleotide polymorphisms (SNPs) were genotyped in 729 African Amer ...[more]

PMID: 20538960

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Project description:There are differences in sleep duration between Blacks/African-Americans and Whites/European-Americans. Recently, we found differences between these ancestry groups in the circadian system, such as circadian period and the magnitude of phase shifts. Here we document the role of ancestry on sleep and cognitive performance before and after a 9-h advance in the sleep/wake schedule similar to flying east or having a large advance in sleep times due to shiftwork, both of which produce extreme circadian misalignment. Non-Hispanic African and European-Americans (N = 20 and 17 respectively, aged 21-43 years) were scheduled to four baseline days each with 8 h time in bed based on their habitual sleep schedule. This sleep/wake schedule was then advanced 9 h earlier for three days. Sleep was monitored using actigraphy. During the last two baseline/aligned days and the first two advanced/misaligned days, beginning 2 h after waking, cognitive performance was measured every 3 h using the Automated Neuropsychological Assessment Metrics (ANAM) test battery. Mixed model ANOVAs assessed the effects of ancestry (African-American or European-American) and condition (baseline/aligned or advanced/misaligned) on sleep and cognitive performance. There was decreased sleep and impaired performance in both ancestry groups during the advanced/misaligned days compared to the baseline/aligned days. In addition, African-Americans obtained less sleep than European-Americans, especially on the first two days of circadian misalignment. Cognitive performance did not differ between African-Americans and European-Americans during baseline days. During the two advanced/misaligned days, however, African-Americans tended to perform slightly worse compared to European-Americans, particularly at times corresponding to the end of the baseline sleep episodes. Advancing the sleep/wake schedule, creating extreme circadian misalignment, had a greater impact on the sleep of African-Americans than European-Americans. Ancestry differences in sleep appear to be exacerbated when the sleep/wake schedule is advanced, which may have implications for individuals undertaking shiftwork and transmeridian travel.

Dataset Information

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

Publications

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

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