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The UK Biobank is a prospective study of 502,543 individuals, combining extensive phenotypic and genotypic data with streamlined access for researchers around the world(1). Here we describe the release of exome-sequence data for the first 49,960 study participants, revealing approximately 4 million coding variants (of which around 98.6% have a frequency of less than 1%). The data include 198,269 autosomal predicted loss-of-function (LOF) variants, a more than 14-fold increase compared to the imputed sequence. Nearly all genes (more than 97%) had at least one carrier with a LOF variant, and most genes (more than 69%) had at least ten carriers with a LOF variant. We illustrate the power of characterizing LOF variants in this population through association analyses across 1,730 phenotypes. In addition to replicating established associations, we found novel LOF variants with large effects on disease traits, includingPIEZO1on varicose veins,COL6A1on corneal resistance,MEPEon bone density, andIQGAP2andGMPRon blood cell traits. We further demonstrate the value of exome sequencing by surveying the prevalence of pathogenic variants of clinical importance, and show that 2% of this population has a medically actionable variant. Furthermore, we characterize the penetrance of cancer in carriers of pathogenicBRCA1andBRCA2variants. Exome sequences from the first 49,960 participants highlight the promise of genome sequencing in large population-based studies and are now accessible to the scientific community. <br /> Exome sequences from the first 49,960 participants in the UK Biobank highlight the promise of genome sequencing in large population-based studies and are now accessible to the scientific community.
Geophysical datasets sensitive to different physical parameters can be used to improve resolution of Earth's internal structure. Herein, we jointly invert long-period magnetotelluric (MT) data and surface-wave dispersion curves. Our approach is based on a joint inversion using a genetic algorithm for a one-dimensional (1-D) isotropic structure, which we extend to 1-D anisotropic media. We apply our new anisotropic joint inversion to datasets from Central Germany demonstrating the capacity of our joint inversion algorithm to establish a 1-D anisotropic model that fits MT and seismic datasets simultaneously and providing new information regarding the deep structure in Central Germany. The lithosphere/asthenosphere boundary is found at approx. 84 km depth and two main anisotropic layers with coincident most conductive/seismic fast-axis direction are resolved at lower crustal and asthenospheric depths. We also quantify the amount of seismic and electrical anisotropy in the asthenosphere showing an emerging agreement between the two anisotropic coefficients.