Publications

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.

Little is known about the risk factors for peripheral artery disease (PAD) among diabetic patients in Saudi Arabia. We therefore investigated the association of traditional and non-traditional PAD risk factors, as well as clinical markers, with the prevalence of PAD in 598 diabetic patients in Saudi Arabia. PAD was diagnosed as an ankle–brachial index (ABI) <0.9. Information on socio-demographic variables, smoking status, duration of diabetes, and medication were collected by questionnaire. Body weight, height, blood pressure and clinical markers were also measured. The prevalence of PAD in this population was 23.1%. Hypertension (OR (odds ratio) = 2.13, 95% CI: 1.29–3.52), obesity (OR=1.75, 95% CI: 1.13–2.73) and longer duration of diabetes (OR for ≥20 years vs 2–4 years = 3.30, 95% CI: 1.66–6.58) were independently and significantly associated with a higher prevalence of PAD. Participants with the highest quartile of fasting blood glucose and homocysteine levels had a 67% (OR=1.67, 95% CI: 0.89–3.31) and 78% (OR=1.78, 95% CI: 0.87–3.66) higher prevalence of PAD, respectively. Our study identified several important and largely modifiable risk factors for PAD in this Saudi population with diabetes. These findings underscored the importance of reducing cardiovascular risk factors in patients with diabetes.

This paper describes a study of the generation and flow of photocurrent through junctions containing three-dimensional arrays of colloidal CdSe quantum dots (QDs) of either a single size or multiple sizes. The electrodes were indium tin oxide (ITO) covered with a thin layer of poly(3,4-ethylenedioxy-thiophene):poly(styrenesulfonate) (PEDOT:PSS) and a eutectic alloy of Ga and In (EGaIn). We measured the current-voltage characteristics of the junctions in the dark and under illumination, with various sources and wavelengths of excitation, and their photocurrent action spectra. Size-selective photoexcitation of the arrays of multiple sizes of QDs helped to determine (i) the location of the interface at which photoinduced separation of charge occurred, (ii) whether the energy absorbed by the QDs was redistributed before separation of charge, and (iii) the dependence of the photovoltage on the locations of various sizes of QDs within the junction. This research is a step toward the use of QDs for harvesting light and for transporting energy and charge in devices-for example, solar cells and photodetectors-that operate at zero bias.

The A allele of SNP rs11833579 on chromosome 12p13 may play a role in mediating susceptibility to IS in the Han Chinese population in a recessive model. The A-G haplotype is also significantly associated with higher IS risk in the Han Chinese population. However, larger populations are warranted to validate our findings.

Circulating adiponectin has been associated with lower risk of colorectal cancer (CRC). Genome‐wide association studies have identified several single‐nucleotide polymorphisms (SNPs) associated with adiponectin levels. However, it is unclear whether these SNPs are associated with CRC risk. In addition, previous data on SNPs in the adiponectin pathway and their associations with CRC are inconsistent. Therefore, we examined 19 SNPs in genes related to adiponectin or its receptors and their associations with CRC using logistic regression among 7,020 cases and 7,631 controls drawn from ten studies included in the Genetics and Epidemiology of Colorectal Cancer Consortium. Using data from a subset of two large cohort studies, we also assessed the contribution of individual SNPs and an adiponectin genetic score to plasma adiponectin after accounting for lifestyle factors among 2,217 women and 619 men. We did not find any statistically significant association between the 19 adiponectin‐associated SNPs and CRC risk (multivariable‐adjusted odds ratios ranged from 0.89 to 1.05, all p > 0.05). Each SNP explained less than 2.50% of the variance of plasma adiponectin, and the genetic score collectively accounted for 2.95 and 1.42% of the variability of adiponectin in women and men, respectively, after adjustment for age, body mass index, physical activity, smoking, alcohol consumption, regular use of aspirin or nonsteroidal anti‐inflammatory drug and postmenopausal hormone use. In conclusion, our findings do not support an association between known adiponectin‐related common SNPs and CRC incidence. However, known common SNPs account for only a limited proportion of the interindividual variance in circulating adiponectin. Further work is warranted to investigate the relationship between adiponectin and CRC while accounting for other components in the pathway.

We report low-temperature electrical transport studies of chemically synthesized, molecular-scale silicon nanowires. Individual nanowires exhibit Coulomb blockade oscillations characteristic of charge addition to a single nanostructure on length scales up to at least 400 nm. Studies also demonstrate coherent charge transport through discrete single particle quantum levels extending across whole devices, and show that the ground-state spin configuration is consistent with the constant interaction model. In addition, depletion of nanowires suggests that phase coherent single-dot characteristics are accessible in the few-charge regime. These results differ from those for nanofabricated planar silicon devices, which show localization on much shorter length scales, and thus suggest potential for molecular-scale silicon nanowires as building blocks for quantum and conventional electronics.

Introduction: Evidence regarding associations between overall low-carbohydrate diets (LCDs) and the risk of developing type 2 diabetes (T2D) remains to be mixed. In the current analysis, we aimed to prospectively assess associations of various LCDs that emphasize different quality of protein, fat, and carbohydrate with T2D risk in U.S. men and women. Methods: A prospective cohort study was conducted in 203,541 men and women participating in the Nurses’ Health Study (NHS), NHSII, and Health Professionals Follow-Up Study who were free of T2D, cardiovascular disease, and cancer at baseline and were followed for up to >30 years. Five LCD scores based on sources of protein, fat, and carbohydrate differentiated by their qualities were derived every four years based on dietary assessments by a validated food frequency questionnaire. Results: During 5,095,048 person-years of follow-up, 19,675 T2D cases were documented. In the multivariable model, a higher overall LCD score was associated with higher T2D risk in a dose-response manner: the hazard ratio (HR) comparing highest vs. lowest quintile was 1.28 (95% confidence interval: 1.22-1.34; P -trend <0.001). A vegetable-based LCD score that emphasizes vegetable protein and fat intake was associated with 6% lower T2D risk (0.94 [0.90-0.98; P -trend =0.003]), and a healthy LCD score that further de-emphasizes refined carbohydrate intake was associated with 15% lower T2D risk (0.85 [0.81-0.89; P -trend <0.001]). In contrast, LCD scores emphasizing high animal protein and fat intake were associated with higher T2D risk. The HRs (95% CIs) comparing extreme quintiles were 1.35 (1.29-1.42; P -trend <0.001) for an overall animal-based LCD score and 1.39 (1.32-1.46; P -trend <0.001) when such a score that further de-emphasizes whole grain intake. Conclusions: LCDs were not beneficial for the primary prevention of T2D unless they emphasize the quality of the macronutrient compositions.

Background: C-reactive protein (CRP) is associated with risk of coronary heart disease (CHD). Whether CRP is causally associated with CHD or merely a marker of underlying atherosclerosis is uncerta...

Abstract Objectives To prospectively evaluate the joint association of duration of rotating night shift work and lifestyle factors with risk of type 2 diabetes risk, and to quantitatively decompose this joint association to rotating night shift work only, to lifestyle only, and to their interaction. Design Prospective cohort study. Setting Nurses’ Health Study (1988-2012) and Nurses’ Health Study II (1991-2013). Participants 143 410 women without type 2 diabetes, cardiovascular disease, or cancer at baseline. Exposures Rotating night shift work was defined as at least three night shifts per month in addition to day and evening shifts in that month. Unhealthy lifestyles included current smoking, physical activity levels below 30 minutes per day at moderate to vigorous intensity, diet in the bottom three fifths of the Alternate Healthy Eating Index score, and body mass index of 25 or above. Main outcome measures Incident cases of type 2 diabetes were identified through self report and validated by a supplementary questionnaire. Results During 22-24 years of follow-up, 10 915 cases of incident type 2 diabetes occurred. The multivariable adjusted hazard ratios for type 2 diabetes were 1.31 (95% confidence interval 1.19 to 1.44) per five year increment of duration of rotating night shift work and 2.30 (1.88 to 2.83) per unhealthy lifestyle factor (ever smoking, low diet quality, low physical activity, and overweight or obesity). For the joint association of per five year increment rotating night shift work and per unhealthy lifestyle factor with type 2 diabetes, the hazard ratio was 2.83 (2.15 to 3.73) with a significant additive interaction (P for interaction <0.001). The proportions of the joint association were 17.1% (14.0% to 20.8%) for rotating night shift work alone, 71.2% (66.9% to 75.8%) for unhealthy lifestyle alone, and 11.3% (7.3% to 17.3%) for their additive interaction. Conclusions Among female nurses, both rotating night shift work and unhealthy lifestyle were associated with a higher risk of type 2 diabetes. The excess risk of rotating night shift work combined with unhealthy lifestyle was higher than the addition of risk associated with each individual factor. These findings suggest that most cases of type 2 diabetes could be prevented by adhering to a healthy lifestyle, and the benefits could be greater in rotating night shift workers.