Logistic Regression in Case-Control Study

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This is a basic presentation about use of Logistic regression in case-control study of genetics data in R.

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  • Coeffcients are calculated my MLE
  • In order to test hypotheses in logistic regression, we have used the likelihood ratio test and the Wald test.
  • If the confidence interval includes 0 we can say that there is no significant difference between the means of the two populations, at a given level of confidence. The width of the confidence interval gives us some idea about how uncertain we are about the difference in the means. A very wide interval may indicate that more data should be collected before anything definite can be said. A confidence interval that includes 1.0 means that the association between the exposure and outcome could have been found by chance alone and that the association is not statistically significant.
  • Binomial is specifying a choice of variance and link functions. Variance is binomial and link is logit function.
  • Logistic Regression in Case-Control Study

    1. 1. Logistic Regression in Case- Control study using – A statistical tool Satish Gupta
    2. 2. What is R?  The R statistical programming language is a free open source package.  The language is very powerful for writing programs.  Many statistical functions are already built in.  Contributed packages expand the functionality to cutting edge research.
    3. 3. Getting Started  Go to www.r-project.org  Downloads: CRAN (Comprehensive R Archive Network)  Set your Mirror: location close to you.  Select Windows 95 or later, MacOS or UNIX platforms
    4. 4. Getting Started
    5. 5. Basic operators and calculations Comparison operators  equal: ==  not equal: !=  greater/less than: > <  greater/less than or equal: >= <= Example: 1 == 1 # Returns TRUE
    6. 6. Basic operators and calculations Logical operators  AND: & x <- 1:10; y <- 10:1 # Creates the sample vectors 'x' and 'y'. x > y & x > 5 # Returns TRUE where both comparisons return TRUE.  OR: | x == y | x != y # Returns TRUE where at least one comparison is TRUE.  NOT: ! !x > y # The '!' sign returns the negation (opposite) of a logical vector.
    7. 7. Basic operators and calculations Calculations  Four basic arithmetic functions: addition, subtraction, multiplication and division 1 + 1; 1 - 1; 1 * 1; 1 / 1 # Returns results of basic arithmetic calculations.  Calculations on vectors x <- 1:10; sum(x); mean(x), sd(x); sqrt(x) # Calculates for the vector x its sum, mean, standard deviation and square root. x <- 1:10; y <- 1:10; x + y # Calculates the sum for each element in the vectors x and y.
    8. 8. R-Graphics R provides comprehensive graphics utilities for visualizing and exploring scientific data. It includes:  Scatter plots  Line plots  Bar plots  Pie charts  Heatmaps  Venn diagrams  Density plots  Box plots
    9. 9. Data handling in R  Load data: mydata = read.csv(“/path/mydata.csv”)  See data on screen: data(mydata)  See top part of data: head(mydata)  Specific number of rows and column of data: mydata[1:10,1:3]  To get a type of data: class(mydata)  Changing class of data: newdata = as.matrix(mydata)  Summary of data: summary(mydata)  Selecting (KEEPING) variables (columns) newdata = mydata[c(1,3:5)]
    10. 10. Data handling in R  Selecting observations newdata= subset(mydata, age>=20 | age <10, select=c(ID, weight) newdata= subset(mydata, sex==“Male” & age >25, select=weight:income)  Excluding (DROPPING) variables (columns) newdata = mydata[c(-3,-5)] mydata$v3 = NULL
    11. 11. R-Library  There are many tools defined as “package” are present in R for different kind of analysis including data from genetics and genomics.  Depending upon the availability of library, it can be downloaded from two sources Using CRAN (Comprehensive R Archive Network) as: install.packages(“package_name”) Using Bioconductor as: source("http://bioconductor.org/biocLite.R") biocLite(“package_name”)
    12. 12. R-Library  To load a package, library() #Lists all libraries/packages that are available on a system. library(genetics) #Package for genetics data analysis library(help=genetics) #Lists all functions/objects of “genetics” package ?function #Opens documentation of a function
    13. 13. What is Logistic Regression?  Logistic regression describes the relationship between a dichotomous response variable and a set of explanatory variables.  Logistic regression is often used because the relationship between the DV (a discrete variable) and a predictor is non-linear.
    14. 14.  A General Model: Logistic Regression JJ disease disease disease XX p p p βββ +++= − = 110) 1 log()logit( Where: pdisease is the probability that an individual has a particular disease. β0 is the intercept β1, β2 …βJ are the coefficients (effects) of genetic factors X1, X2 …XJ are the variables of genetic factors
    15. 15. Assumptions  Logistic regression does not make any assumptions of normality, linearity, and homogeneity of variance for the independent variables.  Because it does not impose these requirements, it is preferred to discriminant analysis when the data does not satisfy these assumptions.
    16. 16. Questions ??  What is the relative importance of each predictor variable?  How does each predictor variable affect the outcome?  Does a predictor variable make the solution better or worse or have no effect?  Are there interactions among predictors?  Does adding interactions among predictors (continuous or categorical) improve the model?  What is the strength of association between the outcome variable and a set of predictors?  Often in model comparison you want non-significant differences so strength of association is reported for even non-significant effects.
    17. 17. Types of Logistic Regression  Unconditional logistic regression  Conditional logistic regression ** Rule of thumbs  Use conditional logistic regression if matching has been done, and unconditional if there has been no matching.  When in doubt, use conditional because it always gives unbiased results. The unconditional method is said to overestimate the odds ratio if it is not appropriate.
    18. 18. Data Format Status Matset Se_Quartiles GPX1 GPX4 SEP15 TXN2 1 1 <60 CT TT AG AG 0 1 >60 – 70 CC CC GG GG 1 2 <60 TT CC AG AA 0 2 >70 – 80 CC CT GG GG 1 3 >80 CC CC AA AA 0 3 >60 – 70 CT TT GG GG 1 4 <60 CC CC AA AG 0 4 >70 – 80 TT TT GG GG 1 5 >80 CC CC AG AA 0 5 <60 CC CC GG GG 1 6 >70 – 80 CT TT AA AA 0 6 >80 CC CC GG AG 1 7 >60 – 70 TT CC AA AG
    19. 19. Data and Library loading  Load and use data in R (Using Lung cancer data from PLoS One 2013, 8(3):e59051). lung = read.csv(“/path/lung.csv”, sep= “t”, header = TRUE)  Load the library and use data for analysis library(epicalc) use(lung)
    20. 20. Data Analysis  Performing conditional logistic regression (Case vs. Control) clogit_lung = clogit(Status ~ Se_Quartiles + strata(Matset), data = .data) clogistic.display(clogit_lung) OR(95%CI) P(Wald's test) P(LR-test) Quartiles: ref.=<60 <0.001 >60 – 70 0.4(0.15 – 1.09) 0.074 >70 – 80 0.11(0.03 – 0.33) <0.001 >80 0.10(0.03 – 0.34) <0.001
    21. 21. Data Analysis  Performing conditional logistic regression (Case vs. Control), clogit_lung = clogit(Status ~ GPX1+ strata(Matset), data = .data) clogistic.display(clogit_lung) OR(95%CI) P(Wald's test) P(LR-test) GPX1: ref.=CC 0.032 CT 0.44(0.22 – 0.86) 0.017 TT 0.42(0.13 – 1.38) 0.151
    22. 22. Data Analysis  Performing conditional logistic regression (Case vs. Control), clogit_lung = clogit(Status ~ Se_Quartiles + GPX1+ strata(Matset), data = .data) clogistic.display(clogit_lung)   crude OR(95%CI) adj. OR(95%CI) P(Wald's test) P(LR-test) Quartiles: ref.=<60 <0.001 >60 – 70 0.4(0.15 – 1.09) 0.32(0.11 – 0.96) 0.042 >70 – 80 0.11(0.03 – 0.33) 0.09(0.02 – 0.3) <0.001 >80 0.1(0.03 – 0.34) 0.05(0.01 – 0.23) <0.001 GPX1:ref.=CC 0.006 CT 0.44(0.22 – 0.86) 0.26(0.11 – 0.65) 0.004 TT 0.42(0.13 – 1.38) 0.44(0.09 – 2.18) 0.313 Environmental Factor Genetic Factor
    23. 23. Data Analysis  Performing unconditional logistic regression (Case vs. Control), ulogit_lung = glm(Status ~ Se_Quartiles , family=binomial, data = .data) logistic.display(ulogit_lung) OR(95%CI) P(Wald's test) P(LR-test) Quartiles: ref.=<60 <0.001 >60 – 70 0.41 (0.17 – 1.02) 0.054 >70 – 80 0.13 (0.05 – 0.34) <0.001 >80 0.17 (0.07 – 0.42) <0.001
    24. 24. Data Analysis  Performing unconditional logistic regression (Case vs. Control), ulogit_lung = glm(Status ~ GPX1 , family=binomial, data = .data) logistic.display(ulogit_lung) OR(95%CI) P(Wald's test) P(LR-test) Quartiles: ref.=CC 0.034 CT 0.45 (0.24 – 0.85) 0.014 TT 0.44 (0.14 – 1.36) 0.156
    25. 25. Data Analysis  Performing unconditional logistic regression (Case vs. Control), ulogit_lung = glm(Status ~ Se_Quartiles , family=binomial, data = .data) logistic.display(ulogit_lung) crude OR(95%CI) adj. OR(95%CI) P(Wald's test) P(LR-test) Quartiles: ref.=<60 <0.001 >60 – 70 0.41 (0.17 – 1.02) 0.43 (0.17 – 1.08) 0.074 >70 – 80 0.13 (0.05 – 0.34) 0.13 (0.05 – 0.34) <0.001 >80 0.17 (0.07 – 0.42) 0.15 (0.06 – 0.39) <0.001 GPX1:ref.=CC 0.024 CT 0.45 (0.24 – 0.85) 0.40(0.20 – 0.80) 0.01 TT 0.44 (0.14 – 1.36) 0.42 (0.12 – 1.41) 0.161
    26. 26. Something More   Changing the default reference GPX1 = relevel(GPX1, ref = "TT") pack()  Saving the result result = clogistic.display(clogit_lung) write.csv(result$table, file=“path/result.csv“, sep = “t”) write.table(result$table, file=“path/result.xls“, sep = “t”)
    27. 27. Summary: regression models  Regression models can be used to describe the average effect of predictors on outcomes in your data set.  They can tell how likely that the effect is just be due to chance.  They can look at each predictor “adjusting for” the others (estimating what would happen if all others were held constant.)
    28. 28. Thanks to, Prof. Virasakdi Chongsuvivatwong Epidemiology Unit, Faculty of Medicine, Prince of Songkla University, Thailand

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