Hierarchical Generalized Linear Models for Multiple Groups of Rare and Common Variants: Jointly Estimating Group and Individual-Variant Effects

Complex diseases and traits are likely influenced by many common and rare genetic variants and environmental factors. Detecting disease susceptibility variants is a challenging task, especially when their frequencies are low and/or their effects are small or moderate. We propose here a comprehensive hierarchical generalized linear model framework for simultaneously analyzing multiple groups of rare and common variants and relevant covariates. The proposed hierarchical generalized linear models introduce a group effect and a genetic score (i.e., a linear combination of main-effect predictors for genetic variants) for each group of variants, and jointly they estimate the group effects and the weights of the genetic scores. This framework includes various previous methods as special cases, and it can effectively deal with both risk and protective variants in a group and can simultaneously estimate the cumulative contribution of multiple variants and their relative importance. Our computational strategy is based on extending the standard procedure for fitting generalized linear models in the statistical software R to the proposed hierarchical models, leading to the development of stable and flexible tools. The methods are illustrated with sequence data in gene ANGPTL4 from the Dallas Heart Study. The performance of the proposed procedures is further assessed via simulation studies. The methods are implemented in a freely available R package BhGLM (http://www.ssg.uab.edu/bhglm/)

Photo-catalytic conversion of oxygenated hydrocarbons to hydrogen over heteroatom-doped TiO2 catalysts

Here we report a sustainable process for photo-induced hydrogen production from aqueous solutions of oxygenated hydrocarbons. Doping N and B into TiO2 noticeably improves its activity for hydrogen production. The addition of oxygenated hydrocarbons into water serves both as a hydrogen source and as an electron donor, which substantially enhances hydrogen production as compared with that for the photo-catalytic splitting of pure water. Other biomass-derived compounds such as glucose and sucrose are also shown to have potential for hydrogen production by this photo-catalytic conversion

Mediation analysis of racial disparities in triple-negative breast cancer incidence among postmenopausal women

BackgroundTriple-negative breast cancer (TNBC) is disproportionately higher in Black women relative to White women. The objective of this study was to examine to what extent the association between race/ethnicity and risk of TNBC is mediated by potentially modifiable factors.MethodsA total of 128,623 Black and White women aged 50-79 years from the Women's Health Initiative were followed for a mean of 15.8 years. 643 incident TNBC cases (92 Black women and 551 White women) were confirmed by medical record review. Mediation analyses were conducted using an approach under a counterfactual framework.ResultsBlack women had approximately twofold higher risk of TNBC compared with white women (HR = 1.93, 95% CI 1.52-2.45). We observed that 48% of the racial disparity was mediated by metabolic dysfunction defined by having 3 or more cardiometabolic risk factors including elevated waist circumference, having history of diabetes, high cholesterol and hypertension. The racial disparity was not significantly mediated by other factors studied, including socioeconomic, lifestyle or reproductive factors.ConclusionOur study observed that approximately half of the racial disparity between postmenopausal Black and White women in TNBC incidence was driven by metabolic dysfunction

Solvothermal synthesis of N-doped TiO₂ nanotubes for visible-light-responsive photocatalysis

Visible-light-responsive tubular N-doped TiO₂ nanocrystallites were synthesized via an environment-conscious solvothermal treatment of protonated titanate nanotubes in and NH₄Cl/ethanol/water solution