Rare-Variant Studies to Complement Genome-Wide Association Studies

• Published in: Annual review of genomics and human genetics Vol. 19; no. 1; pp. 97 - 112
• Main Authors: Sazonovs, A, Barrett, J.C
• Format: Journal Article
• Language: English
• Published: United States Annual Reviews 31-08-2018; Annual Reviews, Inc
• Subjects: DNA sequencing; fine mapping; Genome-wide association studies; Genomes; GWAS; rare variants; rare variants; fine mapping; GWAS
• ISSN: 1527-8204; 1545-293X
• DOI: 10.1146/annurev-genom-083117-021641

Genome-wide association studies (GWASs) have revolutionized human disease genetics by discovering tens of thousands of associations between common variants and complex diseases. In parallel, huge technological advances in DNA sequencing have made it possible to measure and analyze rare variation in populations. This review considers these two stories and how they have come together. We first review the history of GWASs and sequencing. We then consider how to understand the biological mechanisms that drive signals of strong association in the absence of rare-variant studies. We describe how rare-variant studies complement these approaches and highlight both data generation and statistical challenges in their interpretation. Finally, we consider how certain special study designs, such as those for families and isolated populations, fit in this paradigm.