Genome-wide association studies for complex traits: consensus, uncertainty and challenges

Abstract

Genome-wide association studies are systematic, well-powered surveys to explore the relationships between sites of common genome sequence variation and disease predisposition on a genome-wide scale. The capacity to undertake genome-wide association studies has resulted in spectacular advances in the understanding of the genetic basis of common phenotypes of biomedical importance, such as diabetes, asthma and some cancers. Application of this approach to large, well-characterized data sets has revealed over 50 disease-susceptibility loci and has provided valuable insights into the allelic architecture of multifactorial traits. The implementation of such studies requires meticulous attention to all stages of the experimental process, from the ascertainment of the samples through to analysis and interpretation of the findings. There is considerable potential for a wide variety of errors and biases to result in spurious associations if precautions are not taken. Extensive replication of positive findings remains the best guarantee against erroneous claims of association. The demand for large-scale replication is leading to extensive international collaborations between groups. Nonetheless, substantial challenges remain as researchers seek more complete descriptions of the susceptibility architecture of traits of interest, and to translate the information gathered into improvements in clinical management.