Open AccessValidating, augmenting and refining genome-wide association signals
Author(s) -
John P. A. Ioannidis,
Gilles Thomas,
Mark J. Daly
Publication year - 2009
Publication title -
nature reviews. genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 26.214
H-Index - 365
eISSN - 1471-0064
pISSN - 1471-0056
DOI - 10.1038/nrg2544
Subject(s) - biology , computational biology , replication (statistics) , genome wide association study , phenotype , genetic association , genetics , genome , human genome , gene , single nucleotide polymorphism , genotype , virology
Studies using genome-wide platforms have yielded an unprecedented number of promising signals of association between genomic variants and human traits. This Review addresses the steps required to validate, augment and refine such signals to identify underlying causal variants for well-defined phenotypes. These steps include: large-scale exact replication across both similar and diverse populations; fine mapping and resequencing; determination of the most informative markers and multiple independent informative loci; incorporation of functional information; and improved phenotype mapping of the implicated genetic effects. Even in cases for which replication proves that an effect exists, confident localization of the causal variant often remains elusive.