Agreement in the scoring of respiratory events and sleep among international sleep centers.

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.Abstract STUDY OBJECTIVES: The American Academy of Sleep Medicine (AASM) guidelines for polysomnography (PSG) scoring are increasingly being adopted worldwide, but the agreement among international centers in scoring respiratory events and sleep stages using these guidelines is unknown. We sought to determine the interrater agreement of PSG scoring among international sleep centers. DESIGN: Prospective study of interrater agreement of PSG scoring. SETTING: Nine center-members of the Sleep Apnea Genetics International Consortium (SAGIC). MEASUREMENTS AND RESULTS: Fifteen previously recorded deidentified PSGs, in European Data Format, were scored by an experienced technologist at each site after they were imported into the locally used analysis software. Each 30-sec epoch was manually scored for sleep stage, arousals, apneas, and hypopneas using the AASM recommended criteria. The computer-derived oxygen desaturation index (ODI) was also recorded. The primary outcome for analysis was the intraclass correlation coefficient (ICC) of the apnea-hypopnea index (AHI). The ICCs of the respiratory variables were: AHI = 0.95 (95% confidence interval: 0.91-0.98), total apneas = 0.77 (0.56-0.87), total hypopneas = 0.80 (0.66-0.91), and ODI = 0.97 (0.93-0.99). The kappa statistics for sleep stages were: wake = 0.78 (0.77-0.79), nonrapid eye movement = 0.77 (0.76-0.78), N1 = 0.31 (0.30-0.32), N2 = 0.60 (0.59-0.61), N3 = 0.67 (0.65-0.69), and rapid eye movement = 0.78 (0.77-0.79). The ICC of the arousal index was 0.68 (0.50-0.85). CONCLUSION: There is strong agreement in the scoring of respiratory events among the SAGIC centers. There is also substantial epoch-by-epoch agreement in scoring sleep variables. Our results suggest that centralized scoring of PSGs may not be necessary in future research collaboration among international sites where experienced, well-trained scorers are involved.NHLBI P01 HL094307 HL093463 Tzagournis Medical Research Endowment Funds of The Ohio State Universit

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

A genome-wide association search for type 2 diabetes genes in African Americans.

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations

Frequently used sleep questionnaires in epidemiological and genetic research for obstructive sleep apnea: a review.

Many sleep questionnaires are utilized by the epidemiological and genetic research communities. This paper reviewed sleep-related questions and answers commonly used in epidemiological studies (focused on sleep apnea and snoring), with an emphasis on the utility of the response options. METHODS: A literature search was conducted to identify relevant sleep questionnaires. Questionnaires were limited to the English language and had to include questions specific to snoring or stop breathing during sleep. Questionnaires had to demonstrate a citation count >10 through Web of Science. A comparison of questions and answers, and elements important in the design of good quality instruments was conducted. RESULTS: Fourteen questionnaires met the inclusion criteria for final review. Validation was conducted for many of these instruments, though the methods and validation populations were highly variable. Study sample sizes were also relatively small and differed in methods of data analysis. These questionnaires were very heterogeneous, with only some (n = 6) allowing a "don't know" alternative. Six specified the time period referred to as "past month", one referred to "last three months" and the remaining questionnaires had no specific timeframe. The response alternatives to specific questions were Yes/No (n = 5), wording only like "never", "seldom", "often" (n = 4), or a frequency scale indicating times per week (n = 8). CONCLUSIONS: There is a need for improved standardized instruments not only to capture relevant sleep information but also to allow greater comparability between studies

Agreement in the scoring of respiratory events and sleep among international sleep centers.

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.Abstract STUDY OBJECTIVES: The American Academy of Sleep Medicine (AASM) guidelines for polysomnography (PSG) scoring are increasingly being adopted worldwide, but the agreement among international centers in scoring respiratory events and sleep stages using these guidelines is unknown. We sought to determine the interrater agreement of PSG scoring among international sleep centers. DESIGN: Prospective study of interrater agreement of PSG scoring. SETTING: Nine center-members of the Sleep Apnea Genetics International Consortium (SAGIC). MEASUREMENTS AND RESULTS: Fifteen previously recorded deidentified PSGs, in European Data Format, were scored by an experienced technologist at each site after they were imported into the locally used analysis software. Each 30-sec epoch was manually scored for sleep stage, arousals, apneas, and hypopneas using the AASM recommended criteria. The computer-derived oxygen desaturation index (ODI) was also recorded. The primary outcome for analysis was the intraclass correlation coefficient (ICC) of the apnea-hypopnea index (AHI). The ICCs of the respiratory variables were: AHI = 0.95 (95% confidence interval: 0.91-0.98), total apneas = 0.77 (0.56-0.87), total hypopneas = 0.80 (0.66-0.91), and ODI = 0.97 (0.93-0.99). The kappa statistics for sleep stages were: wake = 0.78 (0.77-0.79), nonrapid eye movement = 0.77 (0.76-0.78), N1 = 0.31 (0.30-0.32), N2 = 0.60 (0.59-0.61), N3 = 0.67 (0.65-0.69), and rapid eye movement = 0.78 (0.77-0.79). The ICC of the arousal index was 0.68 (0.50-0.85). CONCLUSION: There is strong agreement in the scoring of respiratory events among the SAGIC centers. There is also substantial epoch-by-epoch agreement in scoring sleep variables. Our results suggest that centralized scoring of PSGs may not be necessary in future research collaboration among international sites where experienced, well-trained scorers are involved.NHLBI P01 HL094307 HL093463 Tzagournis Medical Research Endowment Funds of The Ohio State Universit

Effects of continuous positive airway pressure on blood pressure in patients with resistant hypertension and obstructive sleep apnea: ameta-analysis

Objective: To systematically analyze the studies that have examined the effect of continuous positive airway pressure (CPAP) on blood pressure (BP) in patients with resistant hypertension and obstructive sleep apnea (OSA).Methods: Design - meta-analysis of observational studies and randomized controlled trials (RCTs) indexed in PubMed and Ovid (All Journals@Ovid). participants: individuals with resistant hypertension and OSA; interventions - CPAP treatment.Results: A total of six studies met the inclusion criteria for preintervention to postintervention analyses. the pooled estimates of mean changes after CPAP treatment for the ambulatory (24-h) SBP and DBP from six studies were -7.21 mmHg [95% confidence interval (CI): -9.04 to -5.38; P < 0.001; I-2 58%) and -4.99 mmHg (95% CI: -6.01 to -3.96; P < 0.001; I-2 31%), respectively. the pooled estimate of the ambulatory SBP and DBP from the four RCTs showed a mean net change of -6.74 mmHg [95% CI: -9.98 to -3.49; P < 0.001; I-2 61%] and -5.94 mmHg (95% CI: -9.40 to -2.47; P = 0.001; I-2 76%), respectively, in favor of the CPAP group.Conclusion: the pooled estimate shows a favorable reduction of BP with CPAP treatment in patients with resistant hypertension and OSA. the effects sizes are larger than those previously reported in patients with OSA without resistant hypertension.NHLBI of the Ohio State University Center for Clinical and Translational ScienceUniv S Carolina, Div Pulm Crit Care & Sleep Med, Columbia, SC 29208 USAOhio State Univ, Wexner Med Ctr, Div Nephrol, Columbus, OH 43210 USAUniversidade Federal de São Paulo, Dept Psicobiol, Disciplina Med & Biol Sono, São Paulo, BrazilUniv Penn, Perelman Sch Med, Renal & Hypertens Div, Philadelphia, PA 19104 USAUniv Penn, Perelman Sch Med, Ctr Sleep & Circadian Neurobiol, Div Sleep Med, Philadelphia, PA 19104 USAUniv Iceland, Sch Hlth Sci, Fac Med, Reykjavik, IcelandCharite, Ctr Sleep Med, Berlin, GermanyRoyal N Shore Hosp, Dept Resp & Sleep Med, St Leonards, NSW 2065, AustraliaUniv Sydney, Woodcock Inst Med Res, Sydney, NSW 2006, AustraliaTaoyuan Chang Gung Mem Hosp, Dept Internal Med, Gueishan Township, TaiwanOhio State Univ, Wexner Med Ctr, Div Pulm Allergy Crit Care & Sleep Med, Columbus, OH 43210 USAUniversidade Federal de São Paulo, Dept Psicobiol, Disciplina Med & Biol Sono, São Paulo, BrazilNHLBI of the Ohio State University Center for Clinical and Translational Science: P01 HL094307NHLBI of the Ohio State University Center for Clinical and Translational Science: HL093463NHLBI of the Ohio State University Center for Clinical and Translational Science: UL1TR000090Web of Scienc

Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: A multi-ethnic meta-analysis of 45,891 individuals

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10−8- 1.2 ×10−43). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10−4). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10−3, n = 22,044), increased triglycerides (p = 2.6×10−14, n = 93,440), increased waist-to-hip ratio (p = 1.8×10−5, n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10−3, n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL- cholesterol concentrations (p = 4.5×10−13, n = 96,748) and decreased BMI (p = 1.4×10−4, n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance