Publications

Despite the well-known male predominance in the prevalence of obstructive sleep apnoea (OSA), sex differences in the associations between OSA and a comprehensive range of epidemiological factors remain less clear. We examined the prevalence of self-reported OSA in 143 326 females (age 48–93 years) from the Nurses' Health Study (NHS) and NHS-II and 22 896 males from the Health Professionals Follow-up Study (age 65–101 years) in 2012–2013. Multivariable logistic regression was used to estimate the sex-specific prevalence odds ratios (pOR) and 95% confidence intervals of OSA by demographic, anthropometric, lifestyle and comorbidity factors. The overall prevalence of self-reported OSA was 6.4% in females and 13.8% in males. After mutual adjustment, the associations of OSA with physical inactivity, hypertension and daytime sleepiness were stronger in females, whereas the associations with waist circumference and witnessed apnoea were stronger in males (p-heterogeneity <0.01). There were qualitative sex differences in the associations with age (pOR per 5-year increment in females 0.95, 95% CI 0.94–0.96, and males 1.04, 1.01–1.08; p-heterogeneity <0.0001) and marital status (pOR for married versus other in females 0.85, 95% CI 0.81–0.89, and males 1.11, 0.99–1.25; p-heterogeneity <0.0001). Substantial sex differences exist in the associations with various factors, suggesting sex-specific mechanisms in OSA.

Although more than 20 genetic susceptibility loci have been reported for type 2 diabetes (T2D), most reported variants have small to moderate effects and account for only a small proportion of the heritability of T2D, suggesting that the majority of inter-person genetic variation in this disease remains to be determined. We conducted a multistage, genome-wide association study (GWAS) within the Asian Consortium of Diabetes to search for T2D susceptibility markers. From 590,887 SNPs genotyped in 1,019 T2D cases and 1,710 controls selected from Chinese women in Shanghai, we selected the top 2,100 SNPs that were not in linkage disequilibrium (r(2)<0.2) with known T2D loci for in silico replication in three T2D GWAS conducted among European Americans, Koreans, and Singapore Chinese. The 5 most promising SNPs were genotyped in an independent set of 1,645 cases and 1,649 controls from Shanghai, and 4 of them were further genotyped in 1,487 cases and 3,316 controls from 2 additional Chinese studies. Consistent associations across all studies were found for rs1359790 (13q31.1), rs10906115 (10p13), and rs1436955 (15q22.2) with P-values (per allele OR, 95%CI) of 6.49 × 10(-9) (1.15, 1.10-1.20), 1.45 × 10(-8) (1.13, 1.08-1.18), and 7.14 × 10(-7) (1.13, 1.08-1.19), respectively, in combined analyses of 9,794 cases and 14,615 controls. Our study provides strong evidence for a novel T2D susceptibility locus at 13q31.1 and the presence of new independent risk variants near regions (10p13 and 15q22.2) reported by previous GWAS.

OBJECTIVE To examine whether gestational diabetes mellitus (GDM), independent of subsequent diabetes, is an early risk factor for renal impairment long term after the index pregnancy. RESEARCH DESIGN AND METHODS In the Diabetes &amp; Women’s Health (DWH) study (2012–2016), we examined the independent and joint associations of GDM and subsequent diabetes with long-term renal function among 607 women with and 619 women without GDM in the Danish National Birth Cohort (DNBC) index pregnancy (1996–2002). At median follow-up of 13 years after the index pregnancy, serum creatinine (mg/dL) and urinary albumin (mg/L) and creatinine (mg/dL) were measured, from which estimated glomerular filtration rate (eGFR) (mL/min/1.73 m2) and urinary albumin-to-creatinine ratio (UACR) (mg/g) were derived. RESULTS Compared with women without GDM or subsequent diabetes, women with a GDM history had significantly higher eGFR even if they had not subsequently developed diabetes (adjusted β-coefficient [95% CI] = 3.3 [1.7, 5.0]). Women who had a GDM history and later developed diabetes (n = 183) also had significantly higher UACR [exponent β = 1.3 [95% CI 1.1, 1.6]) and an increased risk of elevated UACR (≥20 mg/g) [adjusted relative risk [95% CI] = 2.3 [1.1, 5.9]) compared with women with neither. After adjusting for potential confounders including prepregnancy BMI and hypertension, GDM without subsequent diabetes was not related to UACR. CONCLUSIONS Women who develop GDM in pregnancy were more likely to show increased eGFR levels 9–16 years postpartum, which could indicate early stages of glomerular hyperfiltration and renal damage. However, only those who subsequently developed diabetes showed overt renal damage as evidenced by elevated UACR.

The visualization of the space–charge region in nanowire pn junctions (see image) is presented by far-field optical microscopy. This general approach is a powerful tool for estimates of the carrier distributions and device capacitances. For the case of an n-CdS/p+-Si heterojunction we show that the carrier depletion widths in nanowires deviate from the traditional square-root dependence purely due to electrostatic effects.

Meta-analyses of population-based genome-wide association studies (GWAS) in adults have recently led to the detection of new genetic loci for obesity. Here we aimed to discover additional obesity loci in extremely obese children and adolescents. We also investigated if these results generalize by estimating the effects of these obesity loci in adults and in population-based samples including both children and adults. We jointly analysed two GWAS of 2,258 individuals and followed-up the best, according to lowest p-values, 44 single nucleotide polymorphisms (SNP) from 21 genomic regions in 3,141 individuals. After this DISCOVERY step, we explored if the findings derived from the extremely obese children and adolescents (10 SNPs from 5 genomic regions) generalized to (i) the population level and (ii) to adults by genotyping another 31,182 individuals (GENERALIZATION step). Apart from previously identified FTO, MC4R, and TMEM18, we detected two new loci for obesity: one in SDCCAG8 (serologically defined colon cancer antigen 8 gene; p = 1.85x10(-8) in the DISCOVERY step) and one between TNKS (tankyrase, TRF1-interacting ankyrin-related ADP-ribose polymerase gene) and MSRA (methionine sulfoxide reductase A gene; p = 4.84x10(-7)), the latter finding being limited to children and adolescents as demonstrated in the GENERALIZATION step. The odds ratios for early-onset obesity were estimated at approximately 1.10 per risk allele for both loci. Interestingly, the TNKS/MSRA locus has recently been found to be associated with adult waist circumference. In summary, we have completed a meta-analysis of two GWAS which both focus on extremely obese children and adolescents and replicated our findings in a large followed-up data set. We observed that genetic variants in or near FTO, MC4R, TMEM18, SDCCAG8, and TNKS/MSRA were robustly associated with early-onset obesity. We conclude that the currently known major common variants related to obesity overlap to a substantial degree between children and adults.

Smoking is the strongest environmental risk factor for reduced pulmonary function. The genetic component of various pulmonary traits has also been demonstrated, and at least 26 loci have been reproducibly associated with either FEV 1 (forced expiratory volume in 1 second) or FEV 1 /FVC (FEV 1 /forced vital capacity). Although the main effects of smoking and genetic loci are well established, the question of potential gene-by-smoking interaction effect remains unanswered. The aim of the present study was to assess, using a genetic risk score approach, whether the effect of these 26 loci on pulmonary function is influenced by smoking.We evaluated the interaction between smoking exposure, considered as either ever vs never or pack-years, and a 26-single nucleotide polymorphisms (SNPs) genetic risk score in relation to FEV 1 or FEV 1 /FVC in 50 047 participants of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) and SpiroMeta consortia.We identified an interaction ( βint = -0.036, 95% confidence interval, -0.040 to -0.032, P = 0.00057) between an unweighted 26 SNP genetic risk score and smoking status (ever/never) on the FEV 1 /FVC ratio. In interpreting this interaction, we showed that the genetic risk of falling below the FEV /FVC threshold used to diagnose chronic obstructive pulmonary disease is higher among ever smokers than among never smokers. A replication analysis in two independent datasets, although not statistically significant, showed a similar trend in the interaction effect.This study highlights the benefit of using genetic risk scores for identifying interactions missed when studying individual SNPs and shows, for the first time, that persons with the highest genetic risk for low FEV 1 /FVC may be more susceptible to the deleterious effects of smoking.

OBJECTIVE Elevated lipopolysaccharide-binding protein (LBP), a marker of subclinical endotoxemia, may be involved in the pathogenesis of obesity and metabolic risk. We aimed to investigate the association between plasma LBP and metabolic disorders in apparently healthy Chinese. RESEARCH DESIGN AND METHODS A population-based study including 559 overweight/obese (BMI ≥24.0 kg/m2) and 500 normal-weight (18.0 ≤ BMI &amp;lt;24.0 kg/m2) subjects aged 35–54 years was conducted in Shanghai, China. Fasting plasma glucose, lipid profile, LBP, high-sensitivity C-reactive protein, interleukin-6, high-molecular-weight (HMW) adiponectin, leptin, hepatic enzymes, and body composition were measured. Metabolic syndrome was defined by the updated National Cholesterol Education Program Adult Treatment Panel III criterion for Asian Americans. RESULTS LBP levels were significantly higher in overweight/obese individuals than in normal-weight individuals (geometric mean 27.6 [95% CI 25.2–30.3] vs. 10.0 [9.1–11.1] μg/ml; P &amp;lt; 0.001). After multiple adjustments including BMI, the odds ratios were 3.54 (95% CI 2.05–6.09) and 5.53 (95% CI 2.64–11.59) for metabolic syndrome and type 2 diabetes, respectively, comparing the highest with the lowest LBP quartile. Further adjustments for inflammatory markers almost abolished the significant association of LBP with metabolic syndrome but not that with type 2 diabetes, and controlling for adipokines and hepatic enzymes did not substantially alter the results. CONCLUSIONS Elevated circulating LBP was associated with obesity, metabolic syndrome, and type 2 diabetes in apparently healthy Chinese. These findings suggested a role of lipopolysaccharide via initiation of innate immune mechanism(s) in metabolic disorders. Prospective studies are needed to confirm these results.

Introduction: Skipping meals is an increasingly common practice to lose weight among North American adults of all bodyweights. However, due to a lack of long-term studies, the long-term effect of skipping meals to lose weight on cardiometabolic health outcomes such as a diagnosis of type 2 diabetes mellitus (T2DM) or incident coronary heart disease (CHD) remains unknown, although previous short-term studies of skipping meals and risk factors for T2DM and CHD have suggested plausible biological pathways for a relationship to exist in either direction, protective or harmful. Hypothesis: We assessed the hypotheses that skipping meals to lose weight was associated with long-term risk of incident T2DM and CHD in the Canadian 1995 Nova Scotia Health Survey (NSHS95), and that these associations were influenced by cardiometabolic risk factors. Methods: Skipping meals to lose weight was assessed via questionnaire in a cohort of 2,898 adults in the NSHS95 and was linked to population-based health care administrative databases to determine incidence of T2DM and/or CHD in the following 23 years. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for T2DM and CHD. Results: During 23 years of follow-up, 430 incident cases of T2DM and 632 incident cases of CHD were diagnosed. Compared to participants who did not skip meals to lose weight, those who did skip meals to lose weight (2.7%) had an 87% higher risk of T2DM (multivariable-adjusted HR=1.87, 95% CI: 1.11-3.17). This association was no longer present after adjustment for baseline body mass index (BMI) (HR=1.42, 0.83-2.42). After stratification by BMI, skipping meals was associated with T2DM among participants who had BMI &lt;25 kg/m 2 (n=1,030; HR=4.42, 1.01-19.30) but not among participants with BMIs of 25-29.9 kg/m 2 (n=1,123; HR=1.07, 0.39-2.96) or 30+ kg/m 2 (n=586; HR=1.21, 0.61-2.39). The multivariable-adjusted (including BMI) association was also present within participants with elevated cholesterol (n=1,450; HR=1.88, 1.00-3.53) and high blood pressure (n=1,363; HR=2.07, 1.11-3.85), but not among those without. No significant association was observed between skipping meals to lose weight and CHD risk before (HR=1.14, 0.67-1.96) or after adjustment for BMI (HR=1.05, 0.61-1.81), or within subgroups. Conclusion: These findings suggest that skipping meals to lose weight may be a predictive modifiable risk factor for developing T2DM over time, especially among people with a BMI &lt;25 kg/m 2 , potentially working in connection or iteration with other T2DM risk factors. With the growing number of popular diets that include skipping meals, future studies are warranted to understand perturbations of potential metabolic consequences.