Gender differences in association between expiratory dynamic airway collapse and severity of obstructive sleep apnea.

OBJECTIVES: Repetitive unbalances and tensions generated by inspiratory efforts against an obstructive upper airway during sleep predispose the development of expiratory central airway collapse. In addition, structures of the upper airway between men and women have differences and could be the reasons for differences in obstructive sleep apnea (OSA) prevalence between genders. The present study aimed to evaluate the association between parameters of expiratory dynamic tracheal collapse measured using chest multidetector CT and objectively measured OSA severity between men and women. MATERIALS AND METHODS: A total of 901 participants who underwent chest CT and overnight in-home polysomnography from the Korean Genome and Epidemiology Study were cross-sectionally analyzed (women: 46.2%). The participants were divided into three groups based on OSA severity by apnea-hypopnea index (AHI). Multivariate linear regression analysis was performed to determine the effects of central airway collapse after adjustment for cardiovascular-related covariates. RESULTS: In a multivariate analysis, percentages of expiratory lumen structure reductions involving area, diameter, and perimeter were associated with AHI (all p values < 0.05) and with OSA severity (moderate-to-severe OSA than no OSA: ß = 3.30%, p = 0.03; ß = 2.05%, p = 0.02; ß = 1.97%, p = 0.02, respectively) in women, whereas men had only a greater percentage of expiratory wall thickness reduction in moderate-to-severe OSA than no OSA (ß = 0.72%, p = 0.003). In addition, women with both mild OSA and moderate-to-severe OSA had higher expiratory tracheal collapse than men without OSA, and a moderate effect of sex was observed (p for interaction = 0.007). CONCLUSION: The expiratory dynamic tracheal collapse was independently associated with severity of OSA in women than in men. CLINICAL RELEVANCE STATEMENT: Differences of pharyngeal structures and inherent features of airways by genders may affect the dissimilarities in vulnerability to sleep apnea between men and women. KEY POINTS: • The expiratory dynamic tracheal collapse was independently associated with severity of OSA in women than in men. • Women with over mild OSA had higher expiratory tracheal collapse than men without OSA, and moderate effect of sex was observed. • Structural differences of airway may affect differences in susceptibility of sleep apnea between genders.

Sleep Duration, Sleep Apnea, and Gray Matter Volume.

This study aimed to evaluate the effect of sleep duration on brain structures in the presence versus absence of sleep apnea in middle-aged and older individuals. The study investigated a population-based sample of 2,560 individuals, aged 49-80 years. The presence of sleep apnea and self-reported sleep duration were examined in relation to gray matter volume (GMV) in total and lobar brain regions. We identified ranges of sleep duration associated with maximal GMV using quadratic regression and bootstrap sampling. A significant quadratic association between sleep duration and GMV was observed in total and lobar brain regions of men with sleep apnea. In the fully adjusted model, optimal sleep durations associated with peak GMV between brain regions ranged from 6.7 to 7.0 hours. Shorter and longer sleep durations were associated with lower GMV in total and 4 sub-regions of the brain in men with sleep apnea.

Paravertebral Muscles as Indexes of Sarcopenia and Sarcopenic Obesity: Comparison With Imaging and Muscle Function Indexes and Impact on Cardiovascular and Metabolic Disorders.

OBJECTIVE. The objectives of this study were to propose the use of the cross-sectional area of paravertebral muscle (PMA) and the ratio of the PMA to the cross-sectional area of visceral fat (PVR) as new indexes of sarcopenia or sarcopenic obesity through comparison with existing indexes and to show the clinical associations of PMA and PVR with hypertension and diabetes. SUBJECTS AND METHODS. A total of 1270 participants (608 men and 662 women; mean [± SD] age, 63.57 ± 6.94 years) were recruited from a community-based population of elderly individuals. PMA and PVR were measured on single-slice abdominal CT images. Pearson correlation was used to evaluate the correlation of PMA and PVR with widely used imaging and muscle function indexes of sarcopenia and sarcopenic obesity. Tertile categories of PMA and PVR were evaluated to investigate associations with risks for hypertension and diabetes in men and women, by use of separate multivariable logistic regression models. RESULTS. PMA was correlated with the cross-sectional area of thigh muscle on CT, appendicular skeletal muscle mass (ASM) on dual-energy x-ray absorptiometry, height-adjusted ASM (calculated as ASM divided by the height in meters squared), and body mass index (BMI)-adjusted ASM (calculated as ASM divided by BMI) (p < .01). PMA was also correlated with hand grip strength and gait speeds (p < .01). PVR was correlated with height-adjusted ASM and BMI-adjusted ASM (p < .01). A high PVR significantly decreased the odds ratios for hypertension and diabetes in the unadjusted model and the model adjusted for age, smoking, and drinking status. The ratio of the cross-sectional area of thigh muscle to the cross-sectional area of visceral fat and the BMI-adjusted ASM produced results similar to those of PVR in terms of the odds ratios for hypertension and diabetes. CONCLUSION. Single-slice abdominal CT can supply PMA and visceral fat information together. PMA and PVR were found to be reliable indexes of sarcopenia and sarcopenic obesity. A high PVR was associated with low risks for hypertension and diabetes.

Relationship of obstructive sleep apnoea severity and subclinical systemic atherosclerosis.

Obstructive sleep apnoea (OSA) is a common form of sleep disordered breathing. Untreated OSA might accelerate atherosclerosis, potentially increasing the cardiovascular disease burden in patients. The present study aimed to evaluate the association between objectively measured OSA severity and the presence of subclinical systemic atherosclerosis using noninvasive measurements, including tomographic quantification of the calcium burden.A total of 2157 participants of the Korean Genome and Epidemiology Study, who were free of structural heart disease and underwent both in-home polysomnography and chest computed tomography, were cross-sectionally analysed. Participants were divided into three groups based on the severity of OSA: no OSA (apnoea-hypopnoea index (AHI) <5 events·h-1, n=1096), mild OSA (AHI 5- <15 events·h-1, n=700) and moderate-to-severe OSA (AHI ≥15 events·h-1, n=361). Calcium deposits in the thoracic aorta and coronary arteries were measured by the Agatston score.Participants with moderate-to-severe OSA were 1.6 times (95% CI 1.18-2.15 times; p=0.002) more likely to have ascending thoracic aorta calcification (≥100 units) than those without OSA, after adjustment for cardiovascular risk factors. In addition, the association between moderate-to-severe OSA and ascending thoracic aorta calcification of subjects with higher epicardial fat volume was slightly stronger than that in patients without OSA and in the lowest epicardial fat volume tertile (OR 2.11, 95% CI 1.30-3.43).Severity of OSA in the general population was independently associated with subclinical systemic atherosclerosis. These findings highlight the potential importance of severe OSA, especially in subjects with higher epicardial fat, as a possible predictive factor for systemic atherosclerosis and cardiovascular disease.

Identification of Susceptibility Loci and Genes for Colorectal Cancer Risk.

BACKGROUND & AIMS: Known genetic factors explain only a small fraction of genetic variation in colorectal cancer (CRC). We conducted a genome-wide association study to identify risk loci for CRC. METHODS: This discovery stage included 8027 cases and 22,577 controls of East-Asian ancestry. Promising variants were evaluated in studies including as many as 11,044 cases and 12,047 controls. Tumor-adjacent normal tissues from 188 patients were analyzed to evaluate correlations of risk variants with expression levels of nearby genes. Potential functionality of risk variants were evaluated using public genomic and epigenomic databases. RESULTS: We identified 4 loci associated with CRC risk; P values for the most significant variant in each locus ranged from 3.92 × 10(-8) to 1.24 × 10(-12): 6p21.1 (rs4711689), 8q23.3 (rs2450115, rs6469656), 10q24.3 (rs4919687), and 12p13.3 (rs11064437). We also identified 2 risk variants at loci previously associated with CRC: 10q25.2 (rs10506868) and 20q13.3 (rs6061231). These risk variants, conferring an approximate 10%-18% increase in risk per allele, are located either inside or near protein-coding genes that include transcription factor EB (lysosome biogenesis and autophagy), eukaryotic translation initiation factor 3, subunit H (initiation of translation), cytochrome P450, family 17, subfamily A, polypeptide 1 (steroidogenesis), splA/ryanodine receptor domain and SOCS box containing 2 (proteasome degradation), and ribosomal protein S2 (ribosome biogenesis). Gene expression analyses showed a significant association (P < .05) for rs4711689 with transcription factor EB, rs6469656 with eukaryotic translation initiation factor 3, subunit H, rs11064437 with splA/ryanodine receptor domain and SOCS box containing 2, and rs6061231 with ribosomal protein S2. CONCLUSIONS: We identified susceptibility loci and genes associated with CRC risk, linking CRC predisposition to steroid hormone, protein synthesis and degradation, and autophagy pathways and providing added insight into the mechanism of CRC pathogenesis.

Identification of FAM13A gene associated with the ratio of FEV1 to FVC in Korean population by genome-wide association studies including gene-environment interactions.

Chronic obstructive pulmonary disease (COPD) is a complex, multifactorial disease. Although smoking is a main risk factor for obstructive impairment, not all smokers develop this critical disease. We conducted a genome-wide association study to identify the association between genetic variants and pulmonary function and also examined how these variants relate to lung impairment in accordance with smoking behaviors. Using two community-based cohorts, the Ansan cohort (n=4319) and the Ansung cohort (n=3674), in the Korean Genome Epidemiology Study, we analyzed the association between genetic variants (single-nucleotide polymorphisms and haplotypes) and the ratio of FEV1 to FVC (FEV1/FVC) using multivariate linear regression models. Similar analyses were conducted after stratification by smoking status. Four genome-wide significant signals in the FAM13A gene (the strongest signal at rs2609264, P=1.76 × 10(-7) in a combined set) were associated with FEV1/FVC. For the association with ratio, the effect size in the CTGA haplotype (risk haplotype) was -0.57% (s.e., 0.11; P=2.10 × 10(-7)) as compared with the TCAG haplotype (reference haplotype) in a combined set. There was also a significant interaction of FAM13A haplotypes with heavy smoking on FEV1/FVC (P for interaction=0.028). We confirmed the previously reported association of FAM13A in 4q22.1 with pulmonary function. The FAM13A haplotypes also interacted with heavy smoking to affect the risk of reduced pulmonary function.

Gene-gene interaction analysis identifies a new genetic risk factor for colorectal cancer.

BACKGROUND: Adiponectin levels have been shown to be associated with colorectal cancer (CRC). Furthermore, a newly identified adiponectin receptor, T-cadherin, has been associated with plasma adiponectin levels. Therefore, we investigated the potential for a genetic association between T-cadherin and CRC risk. RESULT: We conducted a case-control study using the Korean Cancer Prevention study-II cohort, which is composed of 325 CRC patients and 977 normal individuals. Study results revealed that rs3865188 in the 5' flanking region of the T-cadherin gene (CDH13) was significantly associated with CRC (p = 0.0474). The odds ratio (OR) for the TT genotype as compared to the TA + AA genotype was 1.577 (p = 0.0144). In addition, the interaction between CDH13 and the adiponectin gene (APN) for CRC risk was investigated using a logistic regression analysis. Among six APN single nucleotide polymorphisms (rs182052, rs17366568, rs2241767, rs3821799, rs3774261, and rs6773957), an interaction with the rs3865188 was found for four (rs2241767, rs3821799, rs3774261, and rs6773957). The group with combined genotypes of TT for rs3865188 and GG for rs377426 displayed the highest risk for CRC development as compared to those with the other genotype combinations. The OR for the TT/GG genotype as compared to the AA/AA genotype was 4.108 (p = 0.004). Furthermore, the plasma adiponectin level showed a correlation with the gene-gene interaction, and the group with the highest risk for CRC had the lowest adiponectin level (median, 4.8 µg/mL for the TT/GG genotype vs.7.835 µg/mL for the AA/AA genotype, p = 0.0017). CONCLUSIONS: The present study identified a new genetic factor for CRC risk and an interaction between CDH13 and APN in CRC risk. These genetic factors may be useful for predicting CRC risk.

A colorectal cancer prediction model using traditional and genetic risk scores in Koreans.

BACKGROUND: Genome-wide association studies have identified numerous single nucleotide polymorphisms (SNPs) as associated with colorectal cancer (CRC) risk in populations of European descent. However, their utility for predicting risk to CRC in Asians remains unknown. A case-cohort study (random sub-cohort N=1,685) from the Korean Cancer Prevention Study-II (KCPS-II) (N=145,842) was used. Twenty-three SNPs identified in previous 47 studies were genotyped on the KCPS-II sub-cohort members. A genetic risk score (GRS) was calculated by summing the number of risk alleles over all SNPs. Prediction models with or without GRS were evaluated in terms of the area under the receiver operating characteristic curve (AUROC) and the continuous net reclassification index (NRI). RESULTS: Seven of 23 SNPs showed significant association with CRC and rectal cancer in Koreans, but not with colon cancer alone. AUROCs (95% CI) for traditional risk score (TRS) alone and TRS plus GRS were 0.73 (0.69-0.78) and 0.74 (0.70-0.78) for CRC, and 0.71 (0.65-0.77) and 0.74 (0.68-0.79) for rectal cancer, respectively. The NRI (95% CI) for a prediction model with GRS compared to the model with TRS alone was 0.17 (-0.05-0.37) for CRC and 0.41 (0.10-0.68) for rectal cancer alone. CONCLUSION: Our results indicate genetic variants may be useful for predicting risk to CRC in the Koreans, especially risk for rectal cancer alone. Moreover, this study suggests effective prediction models for colon and rectal cancer should be developed separately.

Quantitative analysis of lungs and airways with CT in subjects with the chronic obstructive pulmonary disease (COPD) candidate FAM13A gene: case control study for CT quantification in COPD risk gene.

OBJECTIVE: To investigate the relationship between a chronic obstructive pulmonary disease (COPD) candidate gene, based on a genomewide association study, and computed tomographic (CT) quantitative analysis; and to find a phenotype in the COPD candidate FAM13A gene. MATERIALS AND METHODS: This study was conducted in subclinical male smokers between 2 groups with matched age and smoking status; 162 subjects (mean age, 58 years) with risk (CTGA, n = 85) and reference (TCAG, n = 77) diplotypes replicated through genomewide association study underwent chest CT for quantitative analysis of lungs and airways. We analyzed the measures in both the risk and reference groups using a 2-sample t test. RESULTS: Subjects with the risk CTGA diplotype had significantly higher total lung volume and emphysema index than the reference TCAG diplotype (P = 0.04). Mean lung density was significantly lower (P < 0.05) in the risk group. However, in the analysis of airways, wall area, luminal area, wall and lumen area ratio, and mean lung density on expiratory and inspiratory phases, no significant differences between the 2 groups were seen. CONCLUSIONS: There is a strong relationship between CT quantitative analysis and the COPD candidate gene. Furthermore, the CTGA diplotype was associated with emphysema among the phenotypes of COPD.

Association of nightmares with cardio-cerebrovascular disease, hypertension and hyperlipidemia in older adults: A population-based cross-sectional study.

OBJECTIVE: This cross-sectional study investigated the relationship of nightmares with cardio-cerebrovascular disease (CVD), hypertension and hyperlipidemia which are major preceding diseases of CVD in older adults. METHODS: Participants (n = 2824; mean age 63.6 ± 6.6 years, females 49.3%) completed the Disturbing Dream and Nightmare Severity Index (DDNSI), which was used to divide the sample into either the Nightmare or Non-Nightmare group (cut-off score ≥ 10). Demographic information, history of CVD (cerebrovascular disease, myocardial infarction, congestive heart failure, coronary artery disease, and arrhythmia), hypertension, hyperlipidemia, and self-report questionnaires about stress (Perceived Stress Scale), depression (Beck Depression Inventory), sleep quality (Pittsburgh Sleep Quality Index), and insomnia symptoms were also collected. RESULTS: Among the sample, 379 participants (13.4%) reported experiencing nightmares more than once a year, and 73 participants (2.6%) were classified as having nightmare disorder based on DDNSI scores (≥10). 11.3% of participants (n = 319) reported having more than one CVD. Approximately half of the participants reported a history of hypertension (52.1%, n = 1471) and hyperlipidemia (47.7%, n = 1346). Logistic regression analysis indicated the Nightmare group was 2.04 times at higher risk for hyperlipidemia (OR = 2.04, 95% CI 1.22-3.40, p = .006) after controlling for covariates compared to the Non-Nightmare group. Although non-significant, there was a trend toward a higher risk of hypertension in the Nightmare group (OR = 1.67, 95% CI 0.99-2.84, p = .056). CONCLUSIONS: Results of this study indicate frequent nightmares in older adults may be associated with hyperlipidemia, which are risk factors for CVD. Further studies are needed to explore nightmares' directionality and health consequences in an aging population.

Linking brain structure, cognition, and sleep: insights from clinical data.

STUDY OBJECTIVES: To use relatively noisy routinely collected clinical data (brain magnetic resonance imaging (MRI) data, clinical polysomnography (PSG) recordings, and neuropsychological testing), to investigate hypothesis-driven and data-driven relationships between brain physiology, structure, and cognition. METHODS: We analyzed data from patients with clinical PSG, brain MRI, and neuropsychological evaluations. SynthSeg, a neural network-based tool, provided high-quality segmentations despite noise. A priori hypotheses explored associations between brain function (measured by PSG) and brain structure (measured by MRI). Associations with cognitive scores and dementia status were studied. An exploratory data-driven approach investigated age-structure-physiology-cognition links. RESULTS: Six hundred and twenty-three patients with sleep PSG and brain MRI data were included in this study; 160 with cognitive evaluations. Three hundred and forty-two participants (55%) were female, and age interquartile range was 52 to 69 years. Thirty-six individuals were diagnosed with dementia, 71 with mild cognitive impairment, and 326 with major depression. One hundred and fifteen individuals were evaluated for insomnia and 138 participants had an apnea-hypopnea index equal to or greater than 15. Total PSG delta power correlated positively with frontal lobe/thalamic volumes, and sleep spindle density with thalamic volume. rapid eye movement (REM) duration and amygdala volume were positively associated with cognition. Patients with dementia showed significant differences in five brain structure volumes. REM duration, spindle, and slow-oscillation features had strong associations with cognition and brain structure volumes. PSG and MRI features in combination predicted chronological age (R2 = 0.67) and cognition (R2 = 0.40). CONCLUSIONS: Routine clinical data holds extended value in understanding and even clinically using brain-sleep-cognition relationships.

All-cause and major-cause mortality associated with sleep latency in the Korean Genome and Epidemiology Study (KoGES): a population-based prospective cohort study.

BACKGROUND: The all-cause and cause-specific mortality risk associated with sleep latencies in the general adult population is unknown. We aimed to investigate the association of habitual prolonged sleep latency with long-term all-cause and cause-specific mortality in adults. METHODS: The Korean Genome and Epidemiology Study (KoGES) is a population-based prospective cohort study comprising community-dwelling men and women aged 40-69 years from Ansan, South Korea. The cohort was studied bi-annually from April 17, 2003, to Dec 15, 2020, and the current analysis included all individuals who completed the Pittsburgh Sleep Quality Index (PSQI) questionnaire between April 17, 2003, and Feb 23, 2005. The final study population comprised 3757 participants. Data were analysed from Aug 1, 2021, to May 31, 2022. The main exposure was sleep latency groups based on the PSQI questionnaire: fell asleep in 15 min or less, fell asleep in 16-30 min, occasional prolonged sleep latency (fell asleep in >30 min once or twice a week in the past month) and habitual prolonged sleep latency (fell asleep in >60 min more than once a week or fell asleep in >30 min ≥3 times a week, or both) in the past month at baseline. Outcomes were all-cause and cause-specific (cancer, cardiovascular disease, and other causes) mortality reported during the 18-year study period. Cox proportional hazards regression models were used to examine the prospective relationship between sleep latency and all-cause mortality, and competing risk analyses were done to investigate the association of sleep latency with cause-specific mortality. FINDINGS: During a median follow-up of 16·7 years (IQR 16·3-17·4), 226 deaths were reported. After adjusting for demographic characteristics, physical characteristics, lifestyle factors, chronic conditions, and sleep variables, self-reported habitual prolonged sleep latency was associated with an increased risk of all-cause mortality (hazard ratio [HR] 2·22, 95% CI 1·38-3·57) compared to the reference group (those who fell asleep in 16-30 min). In the fully adjusted model, habitual prolonged sleep latency was associated with a more than doubled risk of dying from cancer compared to the reference group (HR 2·74, 95% CI 1·29-5·82). No significant association was observed between habitual prolonged sleep latency and deaths from cardiovascular disease and other causes. INTERPRETATION: In this population-based prospective cohort study, habitual prolonged sleep latency was independently associated with an increased risk of all-cause and cancer-specific mortality in adults (independently of demographic characteristics, lifestyle factors, chronic morbidities, and other sleep variables). Although further studies are warranted to investigate the causality of the relationship, strategies or interventions to prevent habitual prolonged sleep latencies might enhance longevity in the general adult population. FUNDING: Korea Centers for Disease Control and Prevention.

Obstructive sleep apnoea and long-term risk of incident diabetes in the middle-aged and older general population.

Background: Obstructive sleep apnoea (OSA) is associated with increased risk of type 2 diabetes. However, results from large population-based prospective cohort studies are rare. The main aim of the present study was to investigate the relative risk of 8-year incident type 2 diabetes in relation to OSA severity in a prospective cohort study of middle-aged and older adults. Methods: A total of 2918 participants (mean age 59 years) of the Korean Genome and Epidemiology Study (KoGES), who underwent home-based overnight polysomnography at baseline examination between 2011 and 2014, were followed up 4-yearly between 2015-2018 and 2019-2021. A total of 1697 participants were present in both follow-ups. After excluding participants who had diabetes at baseline (n=481), a total of 1216 participants were eligible for the analyses. Results: OSA at baseline was categorised by apnoea-hypopnoea index levels as non-OSA (0-4.9 events·h-1), mild OSA (5.0-14.9 events·h-1) and moderate-severe OSA (≥15.0 events·h-1). Incident type 2 diabetes was identified at each follow-up. Compared with non-OSA, participants with moderate-severe OSA had 1.5 times higher risk of developing type 2 diabetes at the end of the 8-year follow-up after adjusting for potential covariates (relative risk 1.50, 95% CI 1.02-2.21). In the same analytical models for 4-year relative risk of incident type 2 diabetes, none of the OSA groups were at significantly higher risk compared with the non-OSA group. Conclusion: Moderate-severe OSA, a modifiable risk factor, poses a higher risk of incident type 2 diabetes compared with non-OSA over an 8-year period in general middle-aged and older adults.

Correlation between TMJ Space Alteration and Disc Displacement: A Retrospective CBCT and MRI Study.

This study aims to determine if a large anterior and reduced posterior/superior joint space is highly predictable for disc displacement. From patients with temporomandibular disorders symptoms, fifty-two experimental joints and fourteen control joints were included. The cone beam computed tomography (CBCT) images were used to calculate posterior-to-anterior (P-A) and superior-to-anterior (S-A) joint space ratios, while disc position was determined using magnetic resonance imaging (MRI). One-way analysis of covariance test and receiver operating characteristics analysis were carried out. The results showed that among the 52 experimental joints, 45 were diagnosed as disc displacement and 7 as normal disc positions (N). All 14 control joints showed normal disc positions. The P-A ratio was 1.46 ± 0.21, 0.99 ± 0.23, and 0.86 ± 0.30 in the control, N, and DD groups, respectively (p < 0.001). The S-A ratio was 1.80 ± 0.27, 1.44 ± 0.33, and 1.08 ± 0.35 in the control, N, and DD groups, respectively (p < 0.001). When an altered P-A ratio and/or S-A ratio are observed on the CBCT, the diagnosis of disc displacement is quite predictable with high sensitivity and specificity.

Earlier chronotype in midlife as a predictor of accelerated brain aging: a population-based longitudinal cohort study.

STUDY OBJECTIVES: Evidence suggests that sleep-wake cycle disruption could be an early manifestation of neurodegeneration and might even be a risk factor for developing diseases in healthy adults. We investigated the impact of circadian phase change on structural and functional brain deterioration in a late-adulthood population. METHODS: We analyzed the data of 1874 participants (mean age 58.6 ± 6.3 years, 50.3% female) from the Korean Genome and Epidemiology Study, who were identified as cognitively unimpaired. The mid-sleep time on free days corrected for sleep debt on workdays (MSFsc) at baseline was adopted as an indicator of the chronotype and used to categorize the participants into three groups. The relationships between the chronotype and longitudinal changes in the gray matter volume (GMV) and cognitive function were investigated (mean interval: 4.2 ± 0.5 years). RESULTS: The mean MSFsc of the participants was 2:45 am. The earlier MSFsc was linearly associated with smaller right entorhinal GMV (ß [SE] = 0.02 [0.01]; p = .001) and lower visual memory function test scores at baseline. Longitudinally, the earlier MSFsc at baseline was only significantly associated with more rapid atrophy in the temporal lobe (ß [SE] = 0.18 [0.07]; p = .018) and not with other brain lobes or subregions. Moreover, the earlier MSFsc was associated with more deteriorated verbal learning and visual memory function test scores. CONCLUSIONS: An earlier chronotype in midlife, measured using a questionnaire, can be a valuable indicator for individuals who should be closely monitored for the development of neurodegenerative disorders.

Effect of physical activity on the change in carotid intima-media thickness: An 8-year prospective cohort study.

BACKGROUND AND AIMS: There is a demand for longitudinal studies that use both objective and subjective measures of physical activity to investigate the association of physical activity with the change in carotid intima-media thickness (CIMT). In order to investigate such association, we conducted an 8-year follow-up study that used both objective and subjective measures of physical activity. METHODS: This cohort study used subsamples of the ongoing Korean Genome and Epidemiology Study (KoGES). Included participants were between 49 to 79 years of age at baseline. Exclusion criteria included incomplete assessments of pedometer/accelerometer, international physical activity questionnaire (IPAQ), and baseline CIMT. Participants with a history of cardiovascular diseases were further excluded. Linear regression models were used for the main analysis. Age differences were assessed by stratifying the participants into < 60 years and ≥ 60 years. RESULTS: After removing excluded participants, 835 participants were included in the final analysis (age, 59.84 ± 6.53 years; 326 (39.04%) males). 453 participants were < 60 years and 382 participants were ≥ 60 years. The daily total step count was inversely associated with the percent change in overall CIMT over 8-years (ß = -0.015, standard error = 0.007, P = 0.034). This association was present among participants in the < 60-year-old group (ß = -0.026, standard error = 0.010, P = 0.006), but not among participants in the ≥ 60-year-old group (ß = -0.010, standard error = 0.011, P = 0.38). CONCLUSIONS: The findings suggest that taking preemptive actions of increasing physical activity may prevent the incidence of atherosclerosis.

Facial and Intraoral Photographic Traits Related to Sleep Apnea in a Clinical Sample with Genetic Ancestry Analysis.

Rationale: Craniofacial and pharyngeal morphology influences risk for obstructive sleep apnea (OSA). Quantitative photography provides phenotypic information about these anatomical factors and is feasible in large samples. However, whether associations between morphology and OSA severity differ among populations is unknown. Objectives: The aim of this study was to examine this question in a large sample encompassing people from different ancestral backgrounds. Methods: Participants in SAGIC (Sleep Apnea Global Interdisciplinary Consortium) with genotyping data were included (N = 2,393). Associations between photography-based measures and OSA severity were assessed using linear regression, controlling for age, sex, body mass index, and genetic ancestry. Subgroups (on the basis of 1000 Genomes reference populations) were identified: European (EUR), East Asian, American, South Asian, and African (AFR). Interaction tests were used to assess if genetically determined ancestry group modified these relationships. Results: Cluster analysis of genetic ancestry proportions identified four ancestrally defined groups: East Asia (48.3%), EUR (33.6%), admixed (11.7%; 46% EUR, 27% Americas, and 22% AFR), and AFR (6.4%). Multiple anatomical traits were associated with more severe OSA independent of ancestry, including larger cervicomental angle (standardized ß [95% confidence interval (CI)] = 0.11 [0.06-0.16]; P < 0.001), mandibular width (standardized ß [95% CI] = 0.15 [0.10-0.20]; P < 0.001), and tongue thickness (standardized ß [95% CI] = 0.06 [0.02-0.10]; P = 0.001) and smaller airway width (standardized ß [95% CI] = -0.08 [-0.15 to -0.002]; P = 0.043). Other traits, including maxillary and mandibular depth angles and lower face height, demonstrated different associations with OSA severity on the basis of ancestrally defined subgroups. Conclusions: We confirm that multiple facial and intraoral photographic measurements are associated with OSA severity independent of ancestral background, whereas others differ in their associations among the ancestrally defined subgroups.

CLOCK Genetic Variations Are Associated With Age-Related Changes in Sleep Duration and Brain Volume.

BACKGROUND: Although a connection between sleep disruption and brain aging has been documented, biological mechanisms need to be further clarified. Intriguingly, aging is associated with circadian rhythm and/or sleep dysfunction in a key gene regulating circadian rhythm, Circadian Locomotor Output Cycles Kaput (CLOCK), has been linked to both aging-related sleep disturbances and neurodegenerative diseases. This study aims to investigate how CLOCK genetic variation associates with sleep duration changes and/or volumetric brain alteration. METHODS: This population-based cross-sectional study used data from the Korean Genome Epidemiology Study and analyzed sleep characteristics and genetic and brain imaging data in 2 221 participants (mean 58.8 ± 6.8 years, 50.2% male). Eleven single-nucleotide polymorphisms (SNPs) in CLOCK were analyzed using PLINK software v1.09 to test for their association with sleep duration and brain volume. Haplotype analysis was performed by using pair-wise linkage disequilibrium of CLOCK polymorphisms, and multivariate analysis of covariance was for statistical analysis. RESULTS: Decreased sleep duration was associated with several SNPs in CLOCK intronic regions, with the highest significance for rs10002541 (p = 1.58 × 10-5). Five SNPs with the highest significance (rs10002541, rs6850524, rs4580704, rs3805151, rs3749474) revealed that CGTCT was the most prevalent. In the major CGTCT haplotype, decreased sleep duration over time was associated with lower cortical volumes predominantly in frontal and parietal regions. Less common haplotypes (GCCTC/CGTTC) had shorter sleep duration and more decreases in sleep duration over 8 years, which revealed smaller total and gray matter volumes, especially in frontal and temporal regions of the left hemisphere. CONCLUSION: CLOCK genetic variations could be involved in age-related sleep and brain volume changes.

Genome-Wide Association Study of Airway Wall Thickening in a Korean Chronic Obstructive Pulmonary Disease Cohort.

Airway wall thickening (AWT) plays an important pathophysiological role in airway diseases such as chronic obstructive pulmonary disease (COPD). There are only a few studies on the genetic components contributing to AWT in the Korean population. This study aimed to identify AWT-related single-nucleotide polymorphisms (SNPs) using a genome-wide association study (GWAS). We performed GWAS for AWT using the CODA and KUCOPD cohorts. Thereafter, a meta-analysis was performed. Airway wall thickness was measured using automatic segmentation software. The AWT at an internal perimeter of 10 mm (AWT-Pi10) was calculated by the square root of the theoretical airway wall area using the full-width-half-maximum method. We identified a significant SNP (rs11648772, p = 1.41 × 10-8) located in LINC02127, near SALL1. This gene is involved in the inhibition of epithelial-mesenchymal transition in glial cells, and it affects bronchial wall depression in COPD patients. Additionally, we identified other SNPs (rs11970854, p = 1.92 × 10-6; rs16920168, p = 5.29 × 10-6) involved in airway inflammation and proliferation and found that AWT is influenced by these genetic variants. Our study helps identify the genetic cause of COPD in an Asian population and provides a potential basis for treatment.

Heritability Analyses Uncover Shared Genetic Effects of Lung Function and Change over Time.

Genetic influence on lung functions has been identified in previous studies; however, the relative longitudinal effects of genetic factors and their interactions with smoking on lung function remain unclear. Here, we identified the longitudinal effects of genetic variants on lung function by determining single nucleotide polymorphism (SNP) heritability and genetic correlations, and by analyzing interactions with smoking. Subject-specific means and annual change rates were calculated for eight spirometric measures obtained from 6622 Korean adults aged 40−69 years every two years for 14 years, and their heritabilities were estimated separately. Statistically significant (p < 0.05) heritability for the subject-specific means of all spirometric measures (8~32%) and change rates of forced expiratory volume in 1 s to forced vital capacity ratio (FEV1/FVC; 16%) and post-bronchodilator FEV1/FVC (17%) were detected. Significant genetic correlations of the change rate with the subject-specific mean were observed for FEV1/FVC (ρg = 0.64) and post-bronchodilator FEV1/FVC (ρg = 0.47). Furthermore, post-bronchodilator FEV1/FVC showed significant heritability of SNP-by-smoking interaction (hGXS2 = 0.4) for the annual change rate. The GWAS also detected genome-wide significant SNPs for FEV1 (rs4793538), FEV1/FVC (rs2704589, rs62201158, and rs9391733), and post-bronchodilator FEV1/FVC (rs2445936). We found statistically significant evidence of heritability role on the change in lung function, and this was shared with the effects on cross-sectional measurements. We also found some evidence of interaction with smoking for the change of lung function.