Fig. 1 |. Growth in the discovery of disease-associated genetic variation.

The cumulative numbers of genes harbouring variants causal for rare, monogenic diseases and traits and of significant GWAS associations implicated in common, complex diseases and traits are shown. Left, the advent of high-throughput sequencing technologies and availability of reference genomes from diverse populations has supported a fourfold increase in the discovery of rare disease-causing genes between 1999 and 2019. Right, international efforts such as the Human Genome Project and the HapMap Project, combined with GWAS and sequencing studies, have supported identification of more than 60,000 genetic associations across thousands of human diseases and traits. Centre, more recent developments have brought a synthesis of the rareand common-variant approaches based around the combination of sequence-informed analyses in large cohorts. Key events contributing to these themes are depicted in the timeline. GA4GH, Global Alliance for Genomics and Health¹⁶⁰; ExAC, Exome Aggregation Consortium⁵.