Human Genetic Variation and its Contribution to Complex Traits

- Nature Reviews Genetics
Author/s: -Frazer, Kelly A -Murray, Sarah S -Schork, Nicholas J -Topol, Eric J
Journal: Nature Reviews Genetics
Year: 2009
Volume: 10
Pages: 241
Start Page: 241

Over the last decade or so the human genetics field has debated the common disease–common variant hypothesis, which posits that common complex traits are largely due to common variants with small-to-modest affect sizes. The opposing theory, the rare variant hypothesis, posits that common complex traits are the summation of low-frequency, high-penetrance variants.
Genome-wide association (GWA) studies are the most widely used contemporary approach to relate genetic variation to phenotypic diversity. Over the past 2 years these studies have identified statistical association between hundreds of loci across the genome and common complex traits.
Most of the genes or genomic loci that have been identified by GWA studies have not previously been known to be related to the complex trait under investigation. Surprisingly, there have been several instances in which one genomic interval has been associated with two or more seemingly distinct diseases.