A resampling-based approach to multiple testing with uncertainty in phase.

TitleA resampling-based approach to multiple testing with uncertainty in phase.
Publication TypeJournal Article
Year of Publication2007
AuthorsFoulkes AS, DeGruttola VG
JournalInt J Biostat
Volume3
Issue1
PaginationArticle 2
Date Published2007
ISSN1557-4679
KeywordsAlgorithms, Antiretroviral Therapy, Highly Active, Cholesterol, HDL, Computer Simulation, Dyslipidemias, Gene Dosage, Haplotypes, HIV Infections, HIV-1, Humans, Likelihood Functions, Lipase, Models, Genetic, Models, Statistical
Abstract

Characterizing the genetic correlates to complex diseases requires consideration of a large number of potentially informative biological markers. In addition, attention to alignment of alleles within or across chromosomal pairs, commonly referred to as phase, may be essential for uncovering true biological associations. In the context of population based association studies, phase is generally unobservable. Preservation of type-1 error in a setting with multiple testing presents a further analytical challenge. This manuscript combines a likelihood-based approach to handling missing-ness in phase with a resampling method to adjust for multiple testing. Through simulations we demonstrate preservation of the family-wise error rate and reasonable power for detecting associations. The method is applied to a cohort of 626 HIV-1 infected individuals receiving highly active anti-retroviral therapies, to ascertain potential genetic contributions to abnormalities in lipid profiles. The haplotypic effects of 2 genes, hepatic lipase (HL) and endothelial lipase (EL), on high-density lipoprotein cholesterol (HDL-C) are tested.

Alternate JournalInt J Biostat
PubMed ID22550644
Grant ListAI056983 / AI / NIAID NIH HHS / United States
AI38858 / AI / NIAID NIH HHS / United States
AI51164 / AI / NIAID NIH HHS / United States