A scalable and robust variance components method reveals insights into the architecture of gene-environment interactions underlying complex traits.

Understanding the contribution of gene-environment interactions (GxE) to complex trait variation can provide insights into disease mechanisms, explain sources of heritability, and improve genetic risk prediction. While large biobanks with genetic and deep phenotypic data hold promise for obtaining novel insights into GxE, our understanding of GxE architecture in complex traits remains limited. We introduce a method to estimate the proportion of trait variance explained by GxE (GxE heritability) and additive genetic effects (additive heritability) across the genome and within specific genomic annotations. We show that our method is accurate in simulations and computationally efficient for biobank-scale datasets. We applied our method to common array SNPs (MAF ≥1%), fifty quantitative traits, and four environmental variables (smoking, sex, age, and statin usage) in unrelated white British individuals in the UK Biobank. We found 68 trait-E pairs with significant genome-wide GxE heritability (p<0.05/200) with a ratio of GxE to additive heritability of ≈6.8% on average. Analyzing ≈8 million imputed SNPs (MAF ≥0.1%), we documented an approximate 28% increase in genome-wide GxE heritability compared to array SNPs. We partitioned GxE heritability across minor allele frequency (MAF) and local linkage disequilibrium (LD) values, revealing that, like additive allelic effects, GxE allelic effects tend to increase with decreasing MAF and LD. Analyzing GxE heritability near genes highly expressed in specific tissues, we find significant brain-specific enrichment for body mass index (BMI) and basal metabolic rate in the context of smoking and adipose-specific enrichment for waist-hip ratio (WHR) in the context of sex.

Fast kernel-based association testing of non-linear genetic effects for biobank-scale data.

Our knowledge of non-linear genetic effects on complex traits remains limited, in part, due to the modest power to detect such effects. While kernel-based tests offer a versatile approach to test for non-linear relationships between sets of genetic variants and traits, current approaches cannot be applied to Biobank-scale datasets containing hundreds of thousands of individuals. We propose, FastKAST, a kernel-based approach that can test for non-linear effects of a set of variants on a quantitative trait. FastKAST provides calibrated hypothesis tests while enabling analysis of Biobank-scale datasets with hundreds of thousands of unrelated individuals from a homogeneous population. We apply FastKAST to 53 quantitative traits measured across ≈ 300 K unrelated white British individuals in the UK Biobank to detect sets of variants with non-linear effects at genome-wide significance.

Detectability of active triangulation range finder: a solar irradiance approach.

Active triangulation range finders are widely used in a variety of applications such as robotics and assistive technologies. The power of the laser source should be carefully selected in order to satisfy detectability and still remain eye-safe. In this paper, we present a systematic approach to assess the detectability of an active triangulation range finder in an outdoor environment. For the first time, we accurately quantify the background noise of a laser system due to solar irradiance by coupling the Perez all-weather sky model and ray tracing techniques. The model is validated with measurements with a modeling error of less than 14.0%. Being highly generic and sufficiently flexible, the proposed model serves as a guide to define a laser system for any geographical location and microclimate.

Near-field excitation of nanoantenna resonance.

An array of paired elliptic nanoparticles designed to enhance local fields around the particle pair is fabricated with gold embedded in quartz. Light excites a coupled plasmon resonance in the particle pair and the system acts like a plasmonic nanoantenna providing an enhanced electromagnetic field. Near-field scanning optical microscopy and finite element modeling are used to study the local field effects of the nanoantenna system. Local illumination shows similar resonant properties as plane wave illumination: a strong, localized optical resonance for light polarized parallel to the main, center-to-center axis.