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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.
Great megathrust earthquakes arise from the sudden release of energy accumulated during centuries of interseismic plate convergence. The moment deficit (energy available for future earthquakes) is commonly inferred by integrating the rate of interseismic plate locking over the time since the previous great earthquake. But accurate integration requires knowledge of how interseismic plate locking changes decades after earthquakes, measurements not available for most great earthquakes. Here we reconstruct the post-earthquake history of plate locking at Guafo Island, above the seismogenic zone of the giant 1960 (M-w = 9.5) Chile earthquake, through forward modeling of land-level changes inferred from aerial imagery (since 1974) and measured by GPS (since 1994). We find that interseismic locking increased to similar to 70% in the decade following the 1960 earthquake and then gradually to 100% by 2005. Our findings illustrate the transient evolution of plate locking in Chile, and suggest a similarly complex evolution elsewhere, with implications for the time- and magnitude-dependent probability of future events.
Great megathrust earthquakes arise from the sudden release of energy accumulated during centuries of interseismic plate convergence. The moment deficit (energy available for future earthquakes) is commonly inferred by integrating the rate of interseismic plate locking over the time since the previous great earthquake. But accurate integration requires knowledge of how interseismic plate locking changes decades after earthquakes, measurements not available for most great earthquakes. Here we reconstruct the post-earthquake history of plate locking at Guafo Island, above the seismogenic zone of the giant 1960 (M-w = 9.5) Chile earthquake, through forward modeling of land-level changes inferred from aerial imagery (since 1974) and measured by GPS (since 1994). We find that interseismic locking increased to similar to 70% in the decade following the 1960 earthquake and then gradually to 100% by 2005. Our findings illustrate the transient evolution of plate locking in Chile, and suggest a similarly complex evolution elsewhere, with implications for the time- and magnitude-dependent probability of future events.