Fast and Accurate Genome-Wide Association Test of Multiple Quantitative Traits

Multiple correlated traits are often collected in genetic studies. By jointly analyzing multiple traits, we can increase power by aggregating multiple weak effects and reveal additional insights into the genetic architecture of complex human diseases. In this article, we propose a multivariate linear regression-based method to test the joint association of multiple quantitative traits. It is flexible to accommodate any covariates, has very accurate control of type I errors, and offers very competitive performance. We also discuss fast and accurate significance p value computation especially for genome-wide association studies with small-to-medium sample sizes. We demonstrate through extensive numerical studies that the proposed method has competitive performance. Its usefulness is further illustrated with application to genome-wide association analysis of diabetes-related traits in the Atherosclerosis Risk in Communities (ARIC) study. We found some very interesting associations with diabetes traits which have not been reported before. We implemented the proposed methods in a publicly available R package

Prospects for intermediate mass black hole binary searches with advanced gravitational-wave detectors

We estimated the sensitivity of the upcoming advanced, ground-based gravitational-wave observatories (the upgraded LIGO and Virgo and the KAGRA interferometers) to coalescing intermediate mass black hole binaries (IMBHB). We added waveforms modeling the gravitational radiation emitted by IMBHBs to detectors' simulated data and searched for the injected signals with the coherent WaveBurst algorithm. The tested binary's parameter space covers non-spinning IMBHBs with source-frame total masses between 50 and 1050 $\text{M}_{\odot}$ and mass ratios between $1/6$ and 1$\,$. We found that advanced detectors could be sensitive to these systems up to a range of a few Gpc. A theoretical model was adopted to estimate the expected observation rates, yielding up to a few tens of events per year. Thus, our results indicate that advanced detectors will have a reasonable chance to collect the first direct evidence for intermediate mass black holes and open a new, intriguing channel for probing the Universe over cosmological scales.Comment: 9 pages, 4 figures, corrected the name of one author (previously misspelled

Risk of Type 2 Diabetes and Obesity Is Differentially Associated with Variation in FTO in Whites and African-Americans in the ARIC Study

Single nucleotide polymorphisms (SNPs) in the fat mass and obesity associated (FTO) gene are associated with body mass index (BMI) in populations of European descent. The FTO rs9939609 variant, first detected in a genome-wide association study of diabetes, conferred an increased disease risk that was abolished after adjustment for BMI, suggesting that the association may be due to variation in adiposity. The relationship between diabetes, four previously identified FTO polymorphisms that span a 19.6-kb genomic region, and obesity was therefore evaluated in the biracial population-based Atherosclerosis Risk in Communities Study with the goal of further refining the association by comparing results between the two ethnic groups. The prevalence of diabetes and obesity (BMI ≥30 kg/m2) was established at baseline, and diabetes was determined by either self-report, a fasting glucose level ≥126 mg/dL, or non-fasting glucose ≥200 mg/dL. There were 1,004 diabetes cases and 10,038 non-cases in whites, and 670 cases and 2,780 non-cases in African-Americans. Differences in mean BMI were assessed by a general linear model, and multivariable logistic regression was used to predict the risk of diabetes and obesity. For white participants, the FTO rs9939609 A allele was associated with an increased risk of diabetes (odds ratio (OR)  = 1.19, p<0.001) and obesity (OR = 1.22, p<0.001) under an additive genetic model that was similar for all of the SNPs analyzed. In African-Americans, only the rs1421085 C allele was a determinant of obesity risk (OR = 1.17, p = 0.05), but was found to be protective against diabetes (OR = 0.79, p = 0.03). Adjustment for BMI did not eliminate any of the observed associations with diabetes. Significant statistical interaction between race and the FTO variants suggests that the effect on diabetes susceptibility may be context dependent

A burst search for gravitational waves from binary black holes

Compact binary coalescence (CBC) is one of the most promising sources of gravitational waves. These sources are usually searched for with matched filters which require accurate calculation of the GW waveforms and generation of large template banks. We present a complementary search technique based on algorithms used in un-modeled searches. Initially designed for detection of un-modeled bursts, which can span a very large set of waveform morphologies, the search algorithm presented here is constrained for targeted detection of the smaller subset of CBC signals. The constraint is based on the assumption of elliptical polarisation for signals received at the detector. We expect that the algorithm is sensitive to CBC signals in a wide range of masses, mass ratios, and spin parameters. In preparation for the analysis of data from the fifth LIGO-Virgo science run (S5), we performed preliminary studies of the algorithm on test data. We present the sensitivity of the search to different types of simulated CBC waveforms. Also, we discuss how to extend the results of the test run into a search over all of the current LIGO-Virgo data set.Comment: 12 pages, 4 figures, 2 tables, submitted for publication in CQG in the special issue for the conference proceedings of GWDAW13; corrected some typos, addressed some minor reviewer comments one section restructured and references updated and correcte

Plasma Surface Modification of Polymer Backsheets: Origins of Future Interfacial Barrier/Backsheet Failure

Flexible polymer substrates coated with inorganic oxide moisture barriers are a potential replacement for glass backsheets in thin film PV modules. Silicon oxynitride (SiOxNy) deposited by PECVD on polyethylene terephthalate (PET) represents one potential new backsheet candidate. Barrier deposition runs at NREL have typically included a nitrogen-rich plasma pretreatment prior to actual barrier deposition with the intention of cleaning the PET surface as well as enhancing adhesion of the SiOxNy barrier film to PET; however, test coupons of PET/barrier/EVA/TPE failed after damp heat exposure. PET substrates exposed to plasma conditions similar to those used in pre-treatment were examined by X-ray photoelectron spectroscopy (XPS) to reveal new low molecular weight PET fragments are created which are volatile upon heating and water soluble. Failure analysis of the coupons determined that the moisture barrier is, in fact, transferred to the encapsulant side

Inpatient and Outpatient Infection as a Trigger of Cardiovascular Disease: The ARIC Study

Background Acute infections are known cardiovascular disease (CVD) triggers, but little is known regarding how CVD risk varies following inpatient versus outpatient infections. We hypothesized that in‐ and outpatient infections are associated with CVD risk and that the association is stronger for inpatient infections. Methods and Results Coronary heart disease (CHD) and ischemic stroke cases were identified and adjudicated in the ARIC (Atherosclerosis Risk in Communities Study). Hospital discharge diagnosis codes and Medicare claims data were used to identify infections diagnosed in in‐ and outpatient settings. A case‐crossover design and conditional logistic regression were used to compare in‐ and outpatient infections among CHD and ischemic stroke cases (14, 30, 42, and 90 days before the event) with corresponding control periods 1 and 2 years previously. A total of 1312 incident CHD cases and 727 incident stroke cases were analyzed. Inpatient infections (14‐day odds ratio [OR]=12.83 [5.74, 28.68], 30‐day OR=8.39 [4.92, 14.31], 42‐day OR=6.24 [4.02, 9.67], and 90‐day OR=4.48 [3.18, 6.33]) and outpatient infections (14‐day OR=3.29 [2.50, 4.32], 30‐day OR=2.69 [2.14, 3.37], 42‐day OR=2.45 [1.97, 3.05], and 90‐day OR=1.99 [1.64, 2.42]) were more common in all CHD case periods compared with control periods and inpatient infection was a stronger CHD trigger for all time periods (P Conclusions In‐ and outpatient infections are associated with CVD risk. Patients with an inpatient infection may be at particularly elevated CVD risk and should be considered potential candidates for CVD prophylaxis