Publications

Abstract Background Multi-phenotype genome-wide association studies (MP-GWAS) of correlated traits have greater power to detect genotype–phenotype associations than single-trait GWAS. However, no multi-phenotype analysis method exists for epigenome-wide association studies (EWAS). Results We extended the SCOPA approach developed by us to “methylSCOPA” software in C++ by ‘reversely’ regressing DNA hyper/hypo-methylation information on a linear combination of phenotypes. We evaluated two models of association between DNA methylation and fasting glucose (FG) and insulin (FI) levels: Model 1, including FG, FI, and three measured potential confounders (body mass index [BMI], fasting serum triglyceride levels [TG], and waist/hip ratio [WHR]), and Model 2, including FG and FI corrected for the effects of BMI, TG, and WHR. Both models were additionally corrected for participant sex and smoking status (current/ever/never). We meta-analyzed the cohort-specific MP-EWAS results with our novel software META-methylSCOPA, mapped genomic locations to CGCh37/hg19, and adopted P <1×10 −7 to denote epigenome-wide significance. We used the Illumina Infinium HumanMethylation450K BeadChip array data from the Northern Finland Birth Cohorts (NFBC) 1966/1986. We quality-controlled the data, regressed out the effects of measured potential confounders, and normalized the methylation signal intensity and FI data. The MP-EWAS included data for 643/457 individuals from NFBC1966 and NFBC1986, respectively (total N=1,100). In Model 1, we detected epigenome-wide significant association in the MP-EWAS meta-analysis at cg13708645 (chr12:121,974,305; P =1.2×10 −8 ) within KDM2B gene. Single-trait effects within KDM2B were on FI, BMI, and WHR. Model with effect on BMI and WHR showed the strongest association at this locus, while effect on FI in single-phenotype analysis was driven by the effect of adiposity. In Model 2, the strongest association was at cg05063096 (chr3:143,689,810; P =2.3×10 −7 ) annotated to C3orf58 with strongest effect on FI in single-trait analysis and multi-phenotype effect on FI and WHI within Model 1. We characterized the effects of established EWAS loci for diabetes and its risk factors and detected suggestive (p<0.01) associations at six markers including PHGDH, TXNIP, SLC7A11, CPT1A, MYO5C and ABCG1 , through the dissection of the multi-phenotype effects in Model 1. Conclusions We implemented MP-EWAS in methylSCOPA and demonstrated its enhanced power over single-trait EWAS for correlated phenotypes in large-scale data.

Existing stretchable, transparent conductors are mostly electronic conductors. They limit the performance of interconnects, sensors, and actuators as components of stretchable electronics and soft machines. We describe a class of devices enabled by ionic conductors that are highly stretchable, fully transparent to light of all colors, and capable of operation at frequencies beyond 10 kilohertz and voltages above 10 kilovolts. We demonstrate a transparent actuator that can generate large strains and a transparent loudspeaker that produces sound over the entire audible range. The electromechanical transduction is achieved without electrochemical reaction. The ionic conductors have higher resistivity than many electronic conductors; however, when large stretchability and high transmittance are required, the ionic conductors have lower sheet resistance than all existing electronic conductors.

Objective: To compare fasting serum lipid concentrations of subjects with schizophrenia with a comparison group. Method: The study sample consists of 5654 members of the northern Finland 1966 birth cohort who participated in the field study with blood samples after overnight fasting and clinical examination in 1997–98. Total cholesterol (TC), high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol, triglycerides (TG) and glucose were analyzed. Analysis of variance were used for comparing differences in lipids means between diagnostic categories. Results: Mean fasting TC in subjects with schizophrenia was 20 mg/dl higher than in the comparison group. TC and TG levels in the group of other psychoses resembled the schizophrenia group. Conclusion: Blood lipid levels in subjects with schizophrenia and other functional psychoses were high. As these persons are at special risk for hyperlipidemia their lipid levels should be regularly monitored, and cholesterol lowering diet, as well as medication, should be considered.

'Petal Effect' published in 'Encyclopedia of Nanotechnology'

In soft devices, complex actuation sequences and precise force control typically require hard electronic valves and microcontrollers. Existing designs for entirely soft pneumatic control systems are capable of either digital or analog operation, but not both, and are limited by speed of actuation, range of pressure, time required for fabrication, or loss of power through pull-down resistors. Using the nonlinear mechanics intrinsic to structures composed of soft materials-in this case, by leveraging membrane inversion and tube kinking-two modular soft components are developed: a piston actuator and a bistable pneumatic switch. These two components combine to create valves capable of analog pressure regulation, simplified digital logic, controlled oscillation, nonvolatile memory storage, linear actuation, and interfacing with human users in both digital and analog formats. Three demonstrations showcase the capabilities of systems constructed from these valves: 1) a wearable glove capable of analog control of a soft artificial robotic hand based on input from a human user's fingers, 2) a human-controlled cushion matrix designed for use in medical care, and 3) an untethered robot which travels a distance dynamically programmed at the time of operation to retrieve an object. This work illustrates pathways for complementary digital and analog control of soft robots using a unified valve design.

Our aim was to identify genetic variants associated with blood pressure (BP) in childhood and adolescence.Genome-wide association study data from participating European ancestry cohorts of the Early Genetics and Lifecourse Epidemiology (EAGLE) Consortium was meta-analyzed across 3 epochs; prepuberty (4-7 years), puberty (8-12 years), and postpuberty (13-20 years). Two novel loci were identified as having genome-wide associations with systolic BP across specific age epochs: rs1563894 (ITGA11, located in active H3K27Ac mark and transcription factor chromatin immunoprecipitation and 5'-C-phosphate-G-3' methylation site) during prepuberty (P=2.86×10(-8)) and rs872256 during puberty (P=8.67×10(-9)). Several single-nucleotide polymorphism clusters were also associated with childhood BP at P<5×10(-3). Using a P value threshold of <5×10(-3), we found some overlap in variants across the different age epochs within our study and between several single-nucleotide polymorphisms in any of the 3 epochs and adult BP-related single-nucleotide polymorphisms.Our results suggest that genetic determinants of BP act from childhood, develop over the lifecourse, and show some evidence of age-specific effects.

ABSTRACT Objective Advances in metabolomics now allow high-throughput biomarker profiling of large population studies. We aimed to identify circulating metabolic biomarkers predictive of type 2 diabetes in young adults. Methods Nuclear magnetic resonance metabolomics was used to quantify 229 metabolic measures in 11,896 individuals from four Finnish cohorts (mean age 33 years, range 24–45). Associations between baseline metabolites and risk of type 2 diabetes onset during 8–15 years of follow-up (392 incident cases) were assessed by logistic regression adjusted for sex, age, body mass index, and fasting glucose. Results Out of 229 metabolic measures, 113 were associated with incident diabetes in meta-analysis of the four cohorts (P&lt;0.0009; odds ratios per 1-SD: 0.59–1.50). Among the strongest predictors of diabetes risk were branched-chained and aromatic amino acids (odds ratios 1.31–1.33), triglyceride fractions within the largest very-low-density lipoprotein particles (VLDL; odds ratios 1.33–1.50)), as well as linoleic omega-6 fatty acids (odds ratio 0.75) and free cholesterol in large high-density lipoprotein particles (HDL; odds ratio 0.59). A biomarker score comprised of phenylalanine, free cholesterol in large HDL, and the ratio of cholesteryl esters to total lipids in large VLDL was predictive of the risk for future diabetes in an independent validation cohort (odds ratio 10.1 [95% confidence intervals 4.2-24.1] comparing individuals in upper vs lower fifth of biomarker score). Adjustment for routine lipids and insulin attenuated the odds ratio to 5.8 [2.2-15.1]. Conclusions Metabolic aberrations across multiple molecular pathways are predictive of the long-term risk of type 2 diabetes in young adults. Comprehensive metabolic profiling may potentially help targeting preventive interventions for young asymptomatic individuals at increased risk for type 2 diabetes.

Convenient and inexpensive methods to pattern the facets of optical fibers with metallic nanostructures would enable many applications. This communication reports a method to generate and transfer arrays of metallic nanostructures to the cleaved facets of optical fibers. The process relies on nanoskiving, in which an ultramicrotome, equipped with a diamond knife, sections epoxy nanostructures coated with thin metallic films and embedded in a block of epoxy. Sectioning produces arrays of nanostructures embedded in thin epoxy slabs, which can be transferred manually to the tips of optical fibers at a rate of approximately 2 min−1, with 88% yield. Etching the epoxy matrices leaves arrays of nanostructures supported directly by the facets of the optical fibers. Examples of structures transferred include gold crescents, rings, high-aspect-ratio concentric cylinders, and gratings of parallel nanowires.