Publications

Abstract Schizophrenia is a highly heritable disease, but despite extensive study, its genetic background remains unresolved. The lack of environmental measures in genetic studies may offer some explanation. In recent Finnish studies, high birth weight was found to increase the risk for familial schizophrenia. We examined the interaction between a polygenic risk score for schizophrenia and high birth weight on social anhedonia and schizophrenia in a general population birth cohort. The study sample included 4223 participants from the 1966 Northern Finland Birth Cohort. As a replication sample we used 256 participants from a systematically collected sample of Finnish schizophrenia families. The polygenic risk score comprised of variants published in the large genome-wide meta-analysis for schizophrenia. We found the association between the polygenic risk score and social anhedonia stronger among those with high birth weight, and the same phenomenon was seen for schizophrenia among women, suggesting a gene-environment interaction. Similar results were found within the replication sample. Our results suggest a role for gene-environment interactions in assessing the risk of schizophrenia. Failure to take environmental effects into account may be one of the reasons why identifying significant SNPs for schizophrenia in genome-wide studies has been challenging.

OBJECTIVE—The purpose of this study was to examine the association between fruit, vegetable, and fruit juice intake and development of type 2 diabetes. RESEARCH DESIGN AND METHODS—A total of 71,346 female nurses aged 38–63 years who were free of cardiovascular disease, cancer, and diabetes in 1984 were followed for 18 years, and dietary information was collected using a semiquantitative food frequency questionnaire every 4 years. Diagnosis of diabetes was self-reported. RESULTS—During follow-up, 4,529 cases of diabetes were documented, and the cumulative incidence of diabetes was 7.4%. An increase of three servings/day in total fruit and vegetable consumption was not associated with development of diabetes (multivariate-adjusted hazard ratio 0.99 [95% CI 0.94–1.05]), whereas the same increase in whole fruit consumption was associated with a lower hazard of diabetes (0.82 [0.72–0.94]). An increase of 1 serving/day in green leafy vegetable consumption was associated with a modestly lower hazard of diabetes (0.91 [0.84–0.98]), whereas the same change in fruit juice intake was associated with an increased hazard of diabetes (1.18 [1.10–1.26]). CONCLUSIONS—Consumption of green leafy vegetables and fruit was associated with a lower hazard of diabetes, whereas consumption of fruit juices may be associated with an increased hazard among women.

Background: Low plasma HDL-cholesterol concentrations are a hallmark of diabetic dyslipidemia. A common polymorphism (514C3T) of the hepatic lipase gene (LIPC), which accounts for up to 30% of the variation in hepatic lipase activity, has been associated with low hepatic lipase activity and high HDL-cholesterol concentrations. Objective: We examined the association between this polymorphism and plasma HDL-cholesterol concentrations and evaluated whether this association was modified by adiposity and dietary fat intake. Design: We followed men aged 40–75 y who participated in the HealthProfessionalsFollow-UpStudyin1986.Among18 159men who returned blood samples by 1994, 780 had confirmed type 2 diabetesatblooddrawingorduringfollow-upto1998andwerefree of cardiovascular disease at blood drawing. Results: After adjustment for age, smoking, alcohol consumption, fastingstatus,glycatedhemoglobinconcentration,physicalactivity, and body mass index, HDL-cholesterol concentrations were significantlyhigherinmenwiththeC/TorT/Tgenotypethaninthosewith the C/C genotype (adjusted x: 40.9 and 38.8 mg/dL, respectively; P 0.01). We observed significant LIPC 514 polymorphism body mass index and LIPC 514 polymorphism saturated fat intake interactions for HDL-cholesterol concentrations (P 0.003 for both). The T allele was associated with higher HDL-cholesterol concentrations only in men who were not overweight or who had higher saturated fat intake. Conclusion:Ourstudysuggeststhattheeffectsof514C3Tofthe LIPC gene on HDL concentrations were modified by saturated fat intake and obesity. Am J Clin Nutr 2005;81:1429–35.

Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P < 5 × 10-8) from the largest single-stage blood pressure (BP) genome-wide association study to date (n = 1,028,980 European individuals). These associations explain more than 60% of single nucleotide polymorphism-based BP heritability. Comparing top versus bottom deciles of polygenic risk scores (PRSs) reveals clinically meaningful differences in BP (16.9 mmHg systolic BP, 95% CI, 15.5-18.2 mmHg, P = 2.22 × 10-126) and more than a sevenfold higher odds of hypertension risk (odds ratio, 7.33; 95% CI, 5.54-9.70; P = 4.13 × 10-44) in an independent dataset. Adding PRS into hypertension-prediction models increased the area under the receiver operating characteristic curve (AUROC) from 0.791 (95% CI, 0.781-0.801) to 0.826 (95% CI, 0.817-0.836, ∆AUROC, 0.035, P = 1.98 × 10-34). We compare the 2,103 loci results in non-European ancestries and show significant PRS associations in a large African-American sample. Secondary analyses implicate 500 genes previously unreported for BP. Our study highlights the role of increasingly large genomic studies for precision health research.

Background— Although heat shock protein 60 (Hsp60) is implicated in the pathogenesis of atherosclerosis, its role in coronary heart disease (CHD) is uncertain. This study explored the influence of circulating Hsp60 on CHD in a large case-control study, as well as the impact of acute myocardial infarction on Hsp60 levels in a prospective study. Methods and Results— Plasma Hsp60 and anti-Hsp60 antibody levels were determined by immunoassay. In the case-control study (1003 patients with CHD, 1003 matched control subjects), Hsp60 levels were higher in patients with CHD and were related to CHD (OR comparing extreme quartiles=4.14, P &lt;0.0001). This association remained after adjustment for traditional risk factors ( P for trend &lt;0.0001). Individuals having high levels of Hsp60 (greater than the median of 160.24 ng/mL) and anti-Hsp60 antibody (greater than the median of 38.42 U/mL) were at a greater risk of CHD than those with low levels (OR 2.30, P &lt;0.0001). Stronger additive effects (OR 14.04, P &lt;0.0001) were apparent at higher Hsp60 and anti-Hsp60 antibody levels (&gt;1000 ng/mL and greater than the median of 38.42 U/mL, respectively). The simultaneous presence of high Hsp60 and anti-Hsp60 antibody levels, current smoking, hypertension, and diabetes were cumulatively associated with CHD. Individuals who had any 4 or more of these 5 factors had an OR of 38.61 for CHD ( P &lt;0.0001) compared with individuals who had none of these factors. For the prospective study, blood was drawn from 20 patients immediately after admission for acute myocardial infarction and 2, 3, and 7 days thereafter. Hsp60 levels were significantly higher on the day of and the day after arrival than 7 days after an acute myocardial infarction ( P =0.011 and P =0.026, respectively). Conclusions— Elevated Hsp60 levels are associated with an increased risk for CHD, and Hsp60 and anti-Hsp60 antibody levels combine to increase this risk. In addition, acute myocardial infarction induces Hsp60 release.

This paper describes the use of a nanoindenter, equipped with a diamond tip, to form patterns of indentations on planar substrates (epoxy, silicon, and SiO(2)). The process is called "Indentation Lithography" (IndL). The indentations have the form of pits and furrows, whose cross-sectional profiles are determined by the shapes of the diamond indenters, and whose dimensions are determined by the applied load and hardness of the substrate. IndL makes it possible to indent hard materials, to produce patterns with multiple levels of relief by changing the loading force, and to control the profiles of the indentations by using indenters with different shapes. This paper also demonstrates the transfer of indented patterns to elastomeric PDMS stamps for soft lithography, and to thin films of evaporated gold or silver. Stripping an evaporated film from an indented template produces patterns of gold or silver pyramids, whose tips concentrate electric fields. Patterns produced by IndL can thus be used as substrates for surface-enhanced Raman scattering (SERS) and for other plasmonic applications.

The subgap excitations known as Andreev levels govern the low-energy physics of hybrid superconductor-semiconductor nanostructures, and lie at the origin of topological superconductivity. A quantitative understanding of their scaling with respect to relevant parameters is, however, still limited. Here, the authors address this issue for the prototypical case of a quantum dot coupled to a superconductor. Experimentally, the authors demonstrate the ability to controllably tune the hybridization of the dot and the superconductor. In addition, they develop a methodology to reliably extract the relevant parameters by numerically adjusting the Anderson model to the experimental data. As a result, they carefully study the scaling of Andreev levels within the parameter space and obtain an experimental phase diagram of the system. Their results show an impressive quantitative agreement with the theory.

Abstract : Predictions of large amplitude roll motions and capsize events have proven to be difficult and include large uncertainty. One of the reasons for this is a lack of knowledge of resultant forces and moments for large roll angles. Currently, the equations used by numerical models to predict forces and moments due to roll motion are based on experimental data performed within a small range of roll amplitudes. A data set of forces and moments is necessary to verify that the model predictions are accurate in the upper ranges, or to develop new models to predict the forces and moments for these larger roll amplitudes. In 2005, the Naval Surface Warfare Center, Carderock Division, tested NSWC Model 5613, a tumblehome hullform, with the primary objective of obtaining model scale constrained seakeeping results to provide information necessary to perform verification of surge, sway, heave forces and motions, and roll, pitch, and yaw moments and motions acting on a surface combatant hull during large amplitude motions and capsize events. This report describes the testing and the resultant acquired data and begins to establish a database defining non-linear forces and moments associated with large amplitude motions and capsize events.