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On the follow‐up of genome‐wide association studies: an overall test for the most promising SNPs
Author(s) -
Lipman Peter J.,
Cho Michael H.,
Bakke Per,
Gulsvik Amund,
Kong Xiangyang,
Lomas David A.,
Anderson Wayne,
Silverman Edwin K.,
Lange Christoph
Publication year - 2011
Publication title -
genetic epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.301
H-Index - 98
eISSN - 1098-2272
pISSN - 0741-0395
DOI - 10.1002/gepi.20578
Subject(s) - genome wide association study , single nucleotide polymorphism , genetic association , genotyping , genetics , computational biology , biology , genotype , gene
Even in large‐scale genome‐wide association studies (GWASs), only a fraction of the true associations are detected at the genome‐wide significance level. When few or no associations reach the significance threshold, one strategy is to follow up on the most promising candidates, i.e. the single nucleotide polymorphisms (SNPs) with the smallest association‐test P ‐values, by genotyping them in additional studies. In this communication, we propose an overall test for GWASs that analyzes the SNPs with the most promising P ‐values simultaneously and therefore allows an early assessment of whether the follow‐up of the selected SNPs is likely promising. We theoretically derive the properties of the proposed overall test under the null hypothesis and assess its power based on simulation studies. An application to a GWAS for chronic obstructive pulmonary disease suggests that there are true association signals among the top SNPs and that an additional follow‐up study is promising. Genet. Epidemiol . 2011. © 2011 Wiley‐Liss, Inc. 35:303‐309, 2011