Global Prevalence and Ethnic Diversity of von Willebrand Disease: An Updated Population-Based Genetic Analysis

von Willebrand disease (VWD) is known as the most common inherited bleeding disorder. Despite this, the prevalence of the disease and its different phenotypes is not well established worldwide and among different ethnic groups. We determined the global VWD prevalence and its distribution across distinct ethnic groups using the largest and most widely used publicly available genetic database. We used available exome/genome sequencing data of 807,162 (730,947 exomes, 76,215 genomes) subjects from the Genome Aggregation Database (gnomAD-v4.1). Based on the allele frequency of 321 documented pathogenic VWF variants that were identified in the gnomAD population, the worldwide prevalence of VWD per 1000 people was estimated to be 11 for type 1 VWD (1.1%), 1.3 for type 2A (0.13%), 1.7 for type 2B (0.17%), and 1.5 for type 2M (0.15%). For the recessive forms of VWD, the global prevalence was estimated to be 31 cases per million for type 2N and 1.2 cases per million for type 3 VWD. Additionally, VWD prevalence was found to vary across different ethnic groups. Considering a global population of approximately 8 billion people, the estimated worldwide prevalence of VWD cases is as follows: 88 million individuals with type 1, 10.4 million with type 2A, 13.6 million with type 2B, 12 million with type 2M, 248,000 with type 2N, and 8,800 with type 3. This population-based genetic prevalence indicates a substantially higher than expected frequency of VWD. This novel finding suggests that a large number of patients remain undiagnosed.