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BACKGROUND: Variant Call Format (VCF) is the standard file format for interchanging genetic variation data and associated quality control metrics. The usual row-wise encoding of the VCF data model (either as text or packed binary) emphasises efficient retrieval of all data for a given variant, but accessing data on a field or sample basis is inefficient. Biobank scale datasets currently available consist of hundreds of thousands of whole genomes and hundreds of terabytes of compressed VCF. Row-wise data storage is fundamentally unsuitable and a more scalable approach is needed.RESULTS: Zarr is a format for storing multi-dimensional data that is widely used across the sciences, and is ideally suited to massively parallel processing. We present the VCF Zarr specification, an encoding of the VCF data model using Zarr, along with fundamental software infrastructure for efficient and reliable conversion at scale. We show how this format is far more efficient than standard VCF based approaches, and competitive with specialised methods for storing genotype data in terms of compression ratios and single-threaded calculation performance. We present case studies on subsets of three large human datasets (Genomics England: =78,195; Our Future Health: =651,050; All of Us: =245,394) along with whole genome datasets for Norway Spruce (=1,063) and SARS-CoV-2 (=4,484,157). We demonstrate the potential for VCF Zarr to enable a new generation of high-performance and cost-effective applications via illustrative examples using cloud computing and GPUs.CONCLUSIONS: Large row-encoded VCF files are a major bottleneck for current research, and storing and processing these files incurs a substantial cost. The VCF Zarr specification, building on widely-used, open-source technologies has the potential to greatly reduce these costs, and may enable a diverse ecosystem of next-generation tools for analysing genetic variation data directly from cloud-based object stores, while maintaining compatibility with existing file-oriented workflows.