Rare-Variant Genome-Wide Association Studies: A New Frontier in Genetic Analysis of Complex Traits

Abstract

Genome-wide association studies have, in the last few years, identified thousands of common genetic variants associated with common complex traits and diseases, implicating many genes not previously known to be involved in the biology of those traits. However, these variants have so far explained little of the population variance in trait values or disease susceptibility. As large-scale genome sequencing efforts have revealed the extent of genetic variation at the low end of the frequency range in human populations, the effects of rare variants have been proposed as an explanation of the ‘missing genetic variance.‘ Improved technologies for genotyping rare variants, including inexpensive whole-genome and whole-exome sequencing and rare-variant genotyping chips, coupled with novel analytical methods, are making genome-wide scans for the effects of rare variants possible, and seem likely to usher in a new era in the genetic analysis of complex traits.

KEYWORDS::

• association tests
• complex traits
• exome chips
• exome sequencing
• genome-wide association study
• genotyping
• rare variants
• whole-genome sequencing

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.