Heritability, weak effects, and rare variants in genomewide association studies

Abstract

In less than 5 years, genomewide association studies (GWASs) 2 have completely changed the landscape of human genetic research. Our increasing knowledge of the human genome sequence and its variation (http:// hapmap.ncbi.nlm.nih.gov/) and technological advances in the design of genotyping microarrays have been instrumental in this evolution; however, an essential factor for success has been the use of large international collaborations for assembling studies that encompass genomewide data for tens or hundreds of thousands of individuals. The number of firmly replicated trait-associated loci that have been identified in GWASs is impressive (http://www.genome.gov/ gwastudies), but the contribution of individual singlenucleotide polymorphisms (SNPs) to the studied phenotypes is weak, with rare exceptions. In this article, this aspect of GWASs and some of its implications are discussed. © 2011 American Association for Clinical Chemistry.