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A review of genetic association studies of obstructive sleep apnea: field synopsis and meta-analysis.

ABSTRACT: Obstructive sleep apnea (OSA) is a multifactorial disorder with a heritable component. We performed a field synopsis of genetic association studies of OSA to synthesize the available evidence.Systematic literature review and meta-analysis.Genetic association studies.We searched multiple databases to identify studies of non-HLA genetic associations in OSA. We assessed the power of the primary studies to identify odds ratios (OR) in a plausible range and performed random effects meta-analyses for genetic associations investigated by at least 3 studies. We explored the consistency of the findings between population- and family-based studies.NoneWe identified a total of 31 population-based case-control studies reporting allele-frequency data on 48 polymorphism-OSA associations. Sample sizes were generally small (median number of cases = 102, 25th-75th percentile = 55-151; median number of controls = 79, 25th-75th percentile = 58-137), and genetic effects were moderate in magnitude (median OR = 1.15, 25th-75th percentile = 0.89-1.40). Studies were severely underpowered to detect ORs as high as 2; only eight comparisons (in 6 studies) had more than 90% power to identify a genetic effect of that magnitude at its current sample size. Four genetic associations had been investigated in ? 3 studies: TNFA (-308 A/G) rs1800629, ACE I/D, APOE ?2, and APOE ?4. Only TNFA rs1800629 was significantly associated with OSA under an allele frequency model (3 studies, odds ratio [OR] = 1.82, 95% confidence interval [CI] 1.26-2.61). These results were robust to alternative genetic models; findings for APOE variants were consistent with those from family-based studies.The developing field of OSA genetics is currently dominated by small and underpowered investigations. Promising findings regarding TNFA rs1800629 need to be replicated in larger studies using more comprehensive genotyping methods.

SUBMITTER: Varvarigou V

PROVIDER: S-EPMC3198201 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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A review of genetic association studies of obstructive sleep apnea: field synopsis and meta-analysis.

Varvarigou Vasileia V Dahabreh Issa J IJ Malhotra Atul A Kales Stefanos N SN

Sleep 20111101 11

<h4>Study objectives</h4>Obstructive sleep apnea (OSA) is a multifactorial disorder with a heritable component. We performed a field synopsis of genetic association studies of OSA to synthesize the available evidence.<h4>Design</h4>Systematic literature review and meta-analysis.<h4>Setting</h4>Genetic association studies.<h4>Patients or participants</h4>We searched multiple databases to identify studies of non-HLA genetic associations in OSA. We assessed the power of the primary studies to ident ...[more]

PMID: 22043116

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Project description:BACKGROUND:Although genetic studies have reported a number of loci associated with cutaneous melanoma (CM) risk, a comprehensive synopsis of genetic association studies published in the field and systematic meta-analysis for all eligible polymorphisms have not been reported. METHODS:We systematically annotated data from all genetic association studies published in the CM field (n = 145), including data from genome-wide association studies (GWAS), and performed random-effects meta-analyses across all eligible polymorphisms on the basis of four or more independent case-control datasets in the main analyses. Supplementary analyses of three available datasets derived from GWAS and GWAS-replication studies were also done. Nominally statistically significant associations between polymorphisms and CM were graded for the strength of epidemiological evidence on the basis of the Human Genome Epidemiology Network Venice criteria. All statistical tests were two-sided. RESULTS:Forty-two polymorphisms across 18 independent loci evaluated in four or more datasets including candidate gene studies and available GWAS data were subjected to meta-analysis. Eight loci were identified in the main meta-analyses as being associated with a risk of CM (P < .05) of which four loci showed a genome-wide statistically significant association (P < 1 × 10(-7)), including 16q24.3 (MC1R), 20q11.22 (MYH7B/PIGU/ASIP), 11q14.3 (TYR), and 5p13.2 (SLC45A2). Grading of the cumulative evidence by the Venice criteria suggested strong epidemiological credibility for all four loci with genome-wide statistical significance and one additional gene at 9p23 (TYRP1). In the supplementary meta-analyses, a locus at 9p21.3 (CDKN2A/MTAP) reached genome-wide statistical significance with CM and had strong epidemiological credibility. CONCLUSIONS:To the best of our knowledge, this is the first comprehensive field synopsis and systematic meta-analysis to identify genes associated with an increased susceptibility to CM.

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A review of genetic association studies of obstructive sleep apnea: field synopsis and meta-analysis.

Publications

A review of genetic association studies of obstructive sleep apnea: field synopsis and meta-analysis.

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