Transcription
matorhaplo.cph (in process) Weighted Cox regression for censored survival outcomes Will depend on haplo.stats package to impute haplotypes Will call cph(., robust TRUE) from Design package Allow stratification and time-varying exposuresBenjamin French (bcfrench@upenn.edu)Simple haplotype analyses in RuseR! 201112 / 17
Conclusions Non-iterative weighted estimationIIValid tests for genetic associationsReliable estimates of modest genetic effects of common haplotypes Regression-based frameworkIIAdjustment for or interaction with environmental exposuresStratification and time-varying exposures in Cox regression Straightforward to implement in RIIhaplo.ccs for binary outcomeshaplo.cph for censored survival outcomesBenjamin French (bcfrench@upenn.edu)Simple haplotype analyses in RuseR! 201113 / 17
TargetMay notexistMostlyknown“Relative risk”HighOur focusLowProbablycan’t befoundRareCommonHaplotype frequencyBenjamin French (bcfrench@upenn.edu)Simple haplotype analyses in RuseR! 201114 / 17
LimitationsOur method and/or software may not be applicable to Related individuals Rare haplotypes Small studiesBenjamin French (bcfrench@upenn.edu)Simple haplotype analyses in RuseR! 201115 / 17
CollaboratorsNandita Mitra, PhDDepartment of Biostatistics and EpidemiologyUniversity of PennsylvaniaThomas P Cappola, MDPenn Cardiovascular InstituteUniversity of PennsylvaniaThomas Lumley, PhDDepartment of StatisticsUniversity of AucklandBenjamin French (bcfrench@upenn.edu)Simple haplotype analyses in RuseR! 201116 / 17
References1. Cappola TP, Matkovich SJ, et al. 2011. Loss-of-function DNAsequence variant in the CLCNKA chloride channel implicatesthe cardio-renal axis in interindividual heart failure risk variation.Proc Natl Acad Sci U S A 108:2456–61.2. French B, Lumley T. 2007. haplo.ccs: Estimate haplotype relativerisks in case-control data. R package 1.3.3. French B, Lumley T, et al. 2006. Simple estimates of haplotyperelative risks in case-control data. Genet Epidemiol 30:485–94.4. Sinnwell JP, Schaid DJ. 2009. haplo.stats: Statistical analysisof haplotypes with traits and covariates when linkage phaseis ambiguous. R package version 1.4.4.5. Stephens M, Donnelly P. 2003. A comparison of Bayesian methodsfor haplotype reconstruction from population genotype data. Am JHum Genet 73:1162–69.Benjamin French (bcfrench@upenn.edu)Simple haplotype analyses in RuseR! 201117 / 17
for haplotype reconstruction from population genotype data. Am J Hum Genet 73:1162{69. Benjamin French (bcfrench@upenn.edu) Simple haplotype analyses in R useR! 2011 17 / 17. Title: Simple haplotype analyses in R Author: Benjamin French, PhD Department of Biostatistics and Epidemiology University of Pennsylvania bcfrench@upenn.edu
