Associ的ation Analysis, Logistic Regression, R and S-PLUS.pptVIP

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2017-01-20 发布于北京
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Associ的ation Analysis, Logistic Regression, R and S-PLUS.ppt

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Association Analysis, Logistic Regression, R and S-PLUS Richard Mott http://bioinformatics.well.ox.ac.uk/lectures/ Logistic Regression in Statistical Genetics Applicable to Association Studies Data: Binary outcomes (eg disease status) Dependent on genotypes [+ sex, environment] Aim is to identify which factors influence the outcome Rigorous tests of statistical significance Flexible modelling language Generalisation of Chi-Squared Test What is R ? Statistical analysis package Free Similar to commercial package S-PLUS Runs on Unix, Windows, Mac Many packages for statistical genetics, microarray analysis available in R Easily Programmable Modelling in R Data for individual labelled i=1…n: Response yi Genotypes gij for markers j=1..m Coding Unphased Genotypes Several possibilities: AA, AG, GG original genotypes 12, 21, 22 1, 2, 3 0, 1, 2 # of G alleles Missing Data NA default in R Using R Load genetic logistic regression tools source(‘logistic.R’) Read data table from file t - read.table(‘geno.dat’, header=TRUE) Column names names(t) t$y response (0,1) t$m1, t$m2, …. Genotypes for each marker Contigency Tables in R ftable(t$y,t$m31) prints the contingency table Chi-Squared Test in R The Logistic Model Prob(Yi=0) = exp(hi)/(1+exp(hi)) hi = Sj xij bj - Linear Predictor xij – Design Matrix (genotypes etc) bj – Model Parameters (to be estimated) Model is investigated by estimating the bj’s by maximum likelihood testing if the estimates are different from 0 The Logistic FunctionProb(Yi=0) = exp(hi)/(1+exp(hi)) Types of genetic effect at a single locus Additive Genotype Model Code genotypes as AA x=0, AG x=1, GG x=2 Linear Predictor h = b0 + xb1 P(Y=0|x) = exp(b0 + xb1)/(1+exp(b0 + xb1)) PAA = P(Y=0|x=0) = exp(b0)/(1+exp(b0)) PAG = P(Y=0|x=1) = exp(b0 + b1)/(1+exp(b0 + b1)) PGG = P(Y=0|x=2) = exp(b0 + 2b1)/(1+exp(b0 + 2b1)) Additive Model: b0 = -2 b1 = 2PAA = 0.12 PAG = 0.50 PGG = 0.88 Additive Model: b0 = 0 b1 = 2PAA = 0.50 PAG = 0.88 PGG = 0.98