genetic architecture

Eyre-Walker A 2010 Genetic architecture of a complex trait and its implications for fitness and genome-wide association studies. PNAS 107:1752-1756.

• each rare mutation tends to contribute more to the variance than each common mutation
• these results may explain why most genome-wide association studies have failed to find associations that explain much of the variance

• a good example is human height
• three separate studies involving approximately 63,000 individuals have identified 54 markers associated with height
• these explain less than 10% of the variation in human height, a trait that has a heritability of 80%