An entropy-based statistic for genomewide association studies.

TitleAn entropy-based statistic for genomewide association studies.
Publication TypeJournal Article
Year of Publication2005
AuthorsZhao, J, Boerwinkle, E, Xiong, M
JournalAm J Hum Genet
Volume77
Issue1
Pagination27-40
Date Published2005 Jul
ISSN0002-9297
KeywordsEntropy, Gene Frequency, Genetic Markers, Haplotypes, Humans, Linkage Disequilibrium, Statistics as Topic
Abstract

Efficient genotyping methods and the availability of a large collection of single-nucleotide polymorphisms provide valuable tools for genetic studies of human disease. The standard chi2 statistic for case-control studies, which uses a linear function of allele frequencies, has limited power when the number of marker loci is large. We introduce a novel test statistic for genetic association studies that uses Shannon entropy and a nonlinear function of allele frequencies to amplify the differences in allele and haplotype frequencies to maintain statistical power with large numbers of marker loci. We investigate the relationship between the entropy-based test statistic and the standard chi2 statistic and show that, in most cases, the power of the entropy-based statistic is greater than that of the standard chi2 statistic. The distribution of the entropy-based statistic and the type I error rates are validated using simulation studies. Finally, we apply the new entropy-based test statistic to two real data sets, one for the COMT gene and schizophrenia and one for the MMP-2 gene and esophageal carcinoma, to evaluate the performance of the new method for genetic association studies. The results show that the entropy-based statistic obtained smaller P values than did the standard chi2 statistic.

DOI10.1086/431243
Alternate JournalAm J Hum Genet
PubMed ID15931594
PubMed Central IDPMC1226192
Grant ListES09912 / ES / NIEHS NIH HHS / United States
HL74735 / HL / NHLBI NIH HHS / United States
IP50AR44888 / AR / NIAMS NIH HHS / United States
P50 AR044888 / AR / NIAMS NIH HHS / United States
R01 HL074735 / HL / NHLBI NIH HHS / United States
R01 ES009912 / ES / NIEHS NIH HHS / United States

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