Genetic analysis of obstructive sleep apnoea discovers a strong association with cardiometabolic health

There is currently limited understanding of the genetic aetiology of obstructive sleep apnoea (OSA). We aimed at identifying genetic loci associated with OSA risk and to test if OSA and its comorbidities share a common genetic background.We conducted the first large-scale genome-wide association study of OSA using FinnGen Study (217 955 individuals) with 16 761 OSA patients identified using nationwide health registries.We estimated 8.3% [0.06–0.11] heritability and identified five loci associated with OSA (p<5.0×10−8): rs4837016 near GTPase activating protein and VPS9 domains 1 (GAPVD1), rs10928560 near C-X-C motif chemokine receptor 4 (CXCR4), rs185932673 near Calcium/calmodulin-dependent protein kinase ID (CAMK1D) and rs9937053 near Fat mass and obesity-associated protein (FTO) - a variant previously associated with body mass index (BMI). In a BMI-adjusted analysis, an association was observed for rs10507084 near Rhabdomyosarcoma 2 associated transcript (RMST)/NEDD1 gamma-tubulin ring complex targeting factor (NEDD1). We found high genetic correlations between OSA and BMI (rg=0.72 [0.62–0.83]) and with comorbidities including hypertension, type 2 diabetes (T2D), coronary heart disease (CHD), stroke, depression, hypothyroidism, asthma and inflammatory rheumatic diseases (IRD) (rg>0.30). Polygenic risk score (PRS) for BMI showed 1.98-fold increased OSA risk between the highest and the lowest quintile and Mendelian randomisation supported a causal relationship between BMI and OSA.Our findings support the causal link between obesity and OSA and joint genetic basis between OSA and comorbidities.

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Genetic analysis of obstructive sleep apnoea discovers a strong association with cardiometabolic health

10.1101/2020.08.04.235994 ◽

2020 ◽

Author(s):

Satu Strausz ◽

Sanni Ruotsalainen ◽

Hanna M. Ollila ◽

Juha Karjalainen ◽

Mary Reeve ◽

...

Keyword(s):

Obstructive Sleep Apnoea ◽

Large Scale ◽

Genome Wide Association Study ◽

Strong Association ◽

Genetic Correlations ◽

Sleep Apnoea ◽

Cardiometabolic Health ◽

Inflammatory Rheumatic Diseases ◽

Polygenic Risk Score ◽

Obstructive Sleep

AbstractThere is currently only limited understanding of the genetic aetiology of obstructive sleep apnoea (OSA). The aim of our study is to identify genetic loci associated with OSA risk and to test if OSA and its comorbidities share a common genetic background.We conducted the first large-scale genome-wide association study of OSA using FinnGen Study (217,955 individuals) with 16,761 OSA patients identified using nationwide health registries.We estimated 8.3% [0.06-0.11] heritability and identified five loci associated with OSA (P < 5.0 × 10−8): rs4837016 near GTPase activating protein and VPS9 domains 1 (GAPVD1), rs10928560 near C-X-C motif chemokine receptor 4 (CXCR4), rs185932673 near Calcium/calmodulin-dependent protein kinase ID (CAMK1D) and rs9937053 near Fat mass and obesity-associated protein (FTO) - a variant previously associated with body mass index (BMI). In a BMI-adjusted analysis, an association was observed for rs10507084 near Rhabdomyosarcoma 2 associated transcript (RMST)/NEDD1 gamma-tubulin ring complex targeting factor (NEDD1).We found genetic correlations between OSA and BMI (rg=0.72 [0.62-0.83]) and with comorbidities including hypertension, type 2 diabetes (T2D), coronary heart disease (CHD), stroke, depression, hypothyroidism, asthma and inflammatory rheumatic diseases (IRD) (rg > 0.30). Polygenic risk score (PRS) for BMI showed 1.98-fold increased OSA risk between the highest and the lowest quintile and Mendelian randomization supported a causal relationship between BMI and OSA.Our findings support the causal link between obesity and OSA and joint genetic basis between OSA and comorbidities.

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Oral Appliance Therapy for Obstructive Sleep Apnoea: State of the Art

Journal of Clinical Medicine ◽

10.3390/jcm8122121 ◽

2019 ◽

Vol 8 (12) ◽

pp. 2121 ◽

Cited By ~ 2

Author(s):

Kate Sutherland ◽

Peter A. Cistulli

Keyword(s):

Health Outcomes ◽

Obstructive Sleep Apnoea ◽

Productivity Loss ◽

Sleep Apnoea ◽

World Health ◽

Cardiometabolic Health ◽

Accident Risk ◽

Sleep Study ◽

Pharyngeal Airway ◽

Obstructive Sleep

Obstructive sleep apnoea (OSA) represents a significant global health burden, with impact on cardiometabolic health, chronic disease, productivity loss and accident risk. Oral appliances (OA) are an effective therapy for OSA and work by enlarging and stabilising the pharyngeal airway to prevent breathing obstructions during sleep. Although recommended in clinical guidelines for OSA therapy, they are often considered only as second-line therapy following positive airway pressure (PAP) therapy failure. There has been a long-standing barrier to selecting OA over PAP therapy due to the inability to be certain about the level of efficacy in individual OSA patients. A range of methods to select OSA patients for OA therapy, based on the outcome of a single sleep study night, have been proposed, although none has been widely validated for clinical use. Emergent health outcome data suggest that equivalent apnoea–hypopnea index reduction may not be necessary to produce the same health benefits of PAP. This may be related to the more favourable adherence to OA therapy, which can now be objectively verified. Data on longer term health outcomes are needed, and there are additional opportunities for device improvement and combination therapy approaches. OAs have an important role in precision care of OSA as a chronic disorder through a multi-disciplinary care team. Future studies on real-world health outcomes following OA therapy are needed.

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Impact of obstructive sleep apnoea on cardiometabolic health in an ageing population in rural South Africa: Building the case for the treatment of sleep disorders in deprived settings

10.1101/2020.11.22.20236000 ◽

2020 ◽

Author(s):

Johanna Roche ◽

Dale Rae ◽

Kirsten Redman ◽

Kristen L Knutson ◽

Malcolm von Schantz ◽

...

Keyword(s):

South Africa ◽

Obstructive Sleep Apnoea ◽

Low Income ◽

Multivariable Analysis ◽

Sleep Apnoea ◽

Rural Setting ◽

Cardiometabolic Health ◽

Ageing Population ◽

Arterial Blood ◽

Obstructive Sleep

AbstractObjectivesThe association between obstructive sleep apnoea (OSA) and increased cardiometabolic risk (CMR) has been well documented in higher-income countries. However, OSA and its association with CMR have not yet been investigated, based on objective measures, in Southern Africa. We measured polysomnography (PSG)-derived sleep characteristics, OSA prevalence and its association with cardiometabolic diseases in a rural, low-income, aging African-ancestry population in South Africa.MethodsSeventy-five participants were recruited. BMI, hypertension, diabetes, dyslipidaemia, and HIV status were determined. A continuous CMR score was calculated using waist circumference (WC), random glucose, HDL-cholesterol, triglycerides, and mean arterial blood pressure. Sleep architecture, arousal index, and apnoea-hypopnea index (AHI) for detection of OSA (AHI≥15) were assessed by home-based PSG. Associations between CMR score and age, sex, socio-economic status (SES), AHI and TST were investigated by multivariable analysis.ResultsIn our sample (53 women, 66.1±10.7y, 12 HIV+), 60.7% were overweight/obese, 61.3% hypertensive and 29.3% had undiagnosed OSA. Being older (p=0.02), having a greater BMI (p=0.02) and higher WC (p<0.01) were associated with OSA. AHI severity (ß=0.011p=0.01) and being a woman (ß=0.369, p=0.01) were independently associated with a greater CMR score in SES- and age-adjusted analyses.ConclusionsIn this ageing South African community with obesity and hypertension, OSA prevalence is alarming and associated with CMR. We demonstrate feasibility of detecting OSA in a rural setting using PSG. Our results highlight the necessity for actively promoting health education and systematic screening and treatment of OSA in this population, to prevent future cardiovascular morbidity, especially among women.

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Distinct severity stages of obstructive sleep apnoea are correlated with unique dyslipidaemia: large-scale observational study

Thorax ◽

10.1136/thoraxjnl-2015-207403 ◽

2016 ◽

Vol 71 (4) ◽

pp. 347-355 ◽

Cited By ~ 23

Author(s):

Jian Guan ◽

Hongliang Yi ◽

Jianyin Zou ◽

Lili Meng ◽

Xulan Tang ◽

...

Keyword(s):

Observational Study ◽

Obstructive Sleep Apnoea ◽

Large Scale ◽

Sleep Apnoea ◽

Obstructive Sleep

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Polygenic risk scores for late smoking initiation associated with the risk of schizophrenia

npj Schizophrenia ◽

10.1038/s41537-020-00126-z ◽

2020 ◽

Vol 6 (1) ◽

Author(s):

Kazutaka Ohi ◽

Daisuke Nishizawa ◽

Yukimasa Muto ◽

Shunsuke Sugiyama ◽

Junko Hasegawa ◽

...

Keyword(s):

Smoking Cessation ◽

Large Scale ◽

Genome Wide Association Study ◽

Genetic Correlations ◽

Smoking Initiation ◽

Risk Scores ◽

Polygenic Risk Score ◽

Polygenic Risk ◽

Intermediate Phenotypes ◽

Smoking Behaviors

AbstractPatients with schizophrenia display characteristic smoking-related behaviors and genetic correlations between smoking behaviors and schizophrenia have been identified in European individuals. However, the genetic etiology of the association remains to be clarified. The present study investigated transethnic genetic overlaps between European-based smoking behaviors and the risk of Japanese schizophrenia by conducting polygenic risk score (PRS) analyses. Large-scale European genome-wide association study (GWAS) datasets (n = 24,114–74,035) related to four smoking-related intermediate phenotypes [(i) smoking initiation, (ii) age at smoking initiation, (iii) smoking quantity, and (iv) smoking cessation] were utilized as discovery samples. PRSs derived from these discovery GWASs were calculated for 332 Japanese subjects [schizophrenia patients, their unaffected first-degree relatives (FRs), and healthy controls (HCs)] as a target sample. Based on GWASs of European smoking phenotypes, we investigated the effects of PRSs on smoking phenotypes and the risk of schizophrenia in the Japanese population. Of the four smoking-related behaviors, the PRSs for age at smoking initiation in Europeans significantly predicted the age at smoking initiation (R2 = 0.049, p = 0.026) and the PRSs for smoking cessation significantly predicted the smoking cessation (R2 = 0.092, p = 0.027) in Japanese ever-smokers. Furthermore, the PRSs related to age at smoking initiation in Europeans were higher in Japanese schizophrenia patients than in the HCs and those of the FRs were intermediate between those of patients with schizophrenia and those of the HCs (R2 = 0.015, p = 0.015). In our target subjects, patients with schizophrenia had a higher mean age at smoking initiation (p = 0.018) and rate of daily smoking initiation after age 20 years (p = 0.023) compared with the HCs. A total of 60.6% of the patients started to smoke before the onset of schizophrenia. These findings suggest that genetic factors affecting late smoking initiation are associated with the risk of schizophrenia.

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