Estimation of the multiple testing burden for genomewide association studies of nearly all common variants

• Published in: Genetic epidemiology Vol. 32; no. 4; pp. 381 - 385
• Main Authors: Pe'er, Itsik, Yelensky, Roman, Altshuler, David, Daly, Mark J.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.05.2008
• Subjects: African Continental Ancestry Group - genetics; association studies; Biometry; Databases, Genetic; Epidemiologic Methods; European Continental Ancestry Group - genetics; Genetic Techniques - statistics & numerical data; Genetic Variation; human genetics; Humans; Models, Genetic; Polymorphism, Single Nucleotide; testing burden
• ISSN: 0741-0395; 1098-2272
• DOI: 10.1002/gepi.20303

Genomewide association studies are an exciting strategy in genetics, recently becoming feasible and harvesting many novel genes linked to multiple phenotypes. Determining the significance of results in the face of testing a genomewide set of multiple hypotheses, most of which are producing noisy, null‐distributed association signals, presents a challenge to the wide community of association researchers. Rather than each study engaging in independent evaluation of significance standards, we have undertaken the task of developing such standards for genomewide significance, based on data collected by the International Haplotype Map Consortium. We report an estimated testing burden of a million independent tests genomewide in Europeans, and twice that number in Africans. We further identify the sensitivity of the testing burden to the required significance level, with implications to staged design of association studies. Genet. Epidemiol. 2008. © 2008 Wiley‐Liss, Inc.