Publications

Although genome-wide association studies (GWAS) have identified hundreds of complex trait loci, the pathomechanisms of most remain elusive. Studying the genetics of risk factors predisposing to disease is an attractive approach to identify targets for functional studies. Intracranial aneurysms (IA) are rupture-prone pouches at cerebral artery branching sites. IA is a complex disease for which GWAS have identified five loci with strong association and a further 14 loci with suggestive association. To decipher potential underlying disease mechanisms, we tested whether there are IA loci that convey their effect through elevating blood pressure (BP), a strong risk factor of IA. We performed a meta-analysis of four population-based Finnish cohorts (n(FIN) = 11 266) not selected for IA, to assess the association of previously identified IA candidate loci (n = 19) with BP. We defined systolic BP (SBP), diastolic BP, mean arterial pressure, and pulse pressure as quantitative outcome variables. The most significant result was further tested for association in the ICBP-GWAS cohort of 200 000 individuals. We found that the suggestive IA locus at 5q23.2 in PRDM6 was significantly associated with SBP in individuals of European descent (p(FIN) = 3.01E-05, p(ICBP-GWAS) = 0.0007, p(ALL) = 8.13E-07). The risk allele of IA was associated with higher SBP. PRDM6 encodes a protein predominantly expressed in vascular smooth muscle cells. Our study connects a complex disease (IA) locus with a common risk factor for the disease (SBP). We hypothesize that common variants in PRDM6 can contribute to altered vascular wall structure, hence increasing SBP and predisposing to IA. True positive associations often fail to reach genome-wide significance in GWAS. Our findings show that analysis of traditional risk factors as intermediate phenotypes is an effective tool for deciphering hidden heritability. Further, we demonstrate that common disease loci identified in a population isolate may bear wider significance.

No abstract is provided for this article.

Background— High consumption of trans fat has been linked to the risk of coronary heart disease (CHD). We assessed the hypothesis that higher trans fatty acid contents in erythrocytes were associated with an elevated risk of CHD in a nested case-control study among US women. Methods and Results— Blood samples were collected from 32 826 participants of the Nurses’ Health Study from 1989 to 1990. During 6 years of follow-up, 166 incident cases of CHD were ascertained and matched with 327 controls. Total trans fatty acid content in erythrocytes was significantly correlated with dietary intake of trans fat (correlation coefficient=0.44, P <0.01) and was associated with increased plasma low-density lipoprotein cholesterol ( P for trend =0.06), decreased plasma high-density lipoprotein cholesterol concentrations ( P for trend <0.01), and increased plasma low-density lipoprotein to high-density lipoprotein ratio ( P for trend <0.01). After adjustment for age, smoking status, and other dietary and lifestyle cardiovascular risk factors, higher total trans fatty acid content in erythrocytes was associated with an elevated risk of CHD. The multivariable relative risks (95% confidence intervals) of CHD from the lowest to highest quartiles of total trans fatty acid content in erythrocytes were 1.0 (reference), 1.6 (0.7 to 3.6), 1.6 (0.7 to 3.4), and 3.3 (1.5 to 7.2) ( P for trend <0.01). The corresponding relative risks were 1.0, 1.1, 1.3, and 3.1 ( P for trend <0.01) for a total of 18:1 trans isomers and 1.0, 1.5, 2.5, and 2.8 ( P for trend <0.01) for a total of 18:2 trans isomers. Conclusions— These biomarker data provide further evidence that high trans fat consumption remains a significant risk factor for CHD after adjustment for covariates.

Microcontact printing was used to form nanometer scale patterns of self-assembled monolayers (SAMs) on amorphous Si, crystalline Si, and SiO2 using octadecyltrichlorosilane (OTS) as the ink and an elastomer as the stamp. The patterns were subsequently transferred into crystalline Si substrates or amorphous Si films using the SAM of OTS as the resist film. Atomic force microscopy was used to characterize the quality of the SAM and the resulting patterns. Using a Si pillar structure as the master, “pancakes” of less than 80 nm in size were formed by over etching of the patterned OTS film on amorphous Si using KOH. The size of the resulting amorphous Si pancakes can be controlled by the etching time.

Abstract Reconfigurable devices, whose shape can be drastically altered, are central to expandable shelters, deployable space structures, reversible encapsulation systems and medical tools and robots. All these applications require structures whose shape can be actively controlled, both for deployment and to conform to the surrounding environment. While most current reconfigurable designs are application specific, here we present a mechanical metamaterial with tunable shape, volume and stiffness. Our approach exploits a simple modular origami-like design consisting of rigid faces and hinges, which are connected to form a periodic structure consisting of extruded cubes. We show both analytically and experimentally that the transformable metamaterial has three degrees of freedom, which can be actively deformed into numerous specific shapes through embedded actuation. The proposed metamaterial can be used to realize transformable structures with arbitrary architectures, highlighting a robust strategy for the design of reconfigurable devices over a wide range of length scales.

The genetic basis of expressive vocabulary in children around 2 years old is poorly understood. Here, the authors show that a genetic variant near the ROBO2 gene is associated with early language acquisition in the general population and highlight a potential genetic link between language-related common genetic variation and a linkage region for dyslexia, speech-sound disorder and reading.

OBJECTIVES: To determine the effect of peanut consumption, as part of the diet on cardiometabolic risk factors and Metabolic Syndrome (MetS) in a Chinese population at risk for developing type 2 diabetes. METHODS: We recruited 224 participants (men and women, ages 46 ± 10 y, BMI 28.0 ± 3.1 kg/m(2)) with central obesity plus at least one additional MetS risk factor. In this randomized, parallel-arm, controlled study, participants were supplemented with either lightly salted peanuts, 2oz (56 g) per day or a calorie-matched control snack (refined grains) for 12 weeks. Peanuts and control snacks were consumed between meals. Anthropometric and metabolic measurements were assessed at baseline, week 6 and week 12. We used paired Student's t-tests to examine within-treatment differences and multivariable linear regression for between-treatment differences with the models adjusted for age, sex and baseline BMI (with the exception of analysis on waist circumference [WC], body weight and BMI). Multivariate logistic regression was used to calculate the reversion rate of MetS. RESULTS: The peanut group and the control group had similar energy intake (peanut: 1872 ± 433 kcal, control: 1906 ± 400 kcal). There were no differences observed between the two groups on WC, body weight, and BMI. Compared to baseline, the peanut group had small but significant reductions in WC (–0.88 ± 0.32 cm, P = 0.006), body weight (–0.41 ± 0.16 kg, P = 0.01), and BMI (–0.14 ± 0.06 kg/m(2), P = 0.01) at week 12. Both groups decreased fasting glucose levels (peanut: 0.32 ± 0.06 mmol/L, P < 0.001; control: 0.28 ± 0.05 mmol/L, P < 0.001) and increased HDL-C levels (peanut: 0.05 ± 0.02 mmol/L, P = 0.001; control: 0.05 ± 0.02 mmol/L, P = 0.002) after 12 weeks. The peanut group decreased triglycerides by −0.34 ± 0.13 mmol/L (P = 0.009) at week 6. There were no effects on LDL-C, total cholesterol or blood pressure. The peanut group had a greater reversion rate of MetS compared to the control group at week 6 (31.7% vs. 17.9%, P = 0.04, Figure 1), which attenuated at week 12 (P = 0.10). CONCLUSIONS: Adding 2oz of peanuts per day to the diet for 12 weeks did not promote weight gain among Chinese adults at risk for type 2 diabetes. Consumption of peanuts may help ameliorate MetS, suggesting that peanuts may be a healthful snack option relative to refined grains. FUNDING SOURCES: This study was supported by the Chinese Academy of Sciences (Grant/Award Number: KJZD-EW-G20-02), and an in kind donation from the Peanut Institute. The finding source had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Supporting Tables, Images and/or Graphs

No abstract is provided for this article.