BSHI 2002 Biostatistics Workshop [MTevfik DORAK]课件.pptVIP

STATISTICAL ANALYSIS OF HLA AND DISEASE ASSOCIATIONS;This workshop will cover categorical data analysis for case-control design and some concepts in population genetics;Why would you do an association study? Disease gene mapping and positional cloning Molecular profiling (to predict susceptibility, outcome, response, prognosis) Basic science (to learn about disease development and subsequently to design diagnostic tests or new treatment);Meaning of an association Population stratification (confounding by ethnicity) or other spurious associations Linkage disequilibrium (confounding by locus) Direct involvement in the disease process;Cross-validation of results Replication (population level and/or family-based) Functional studies Split the sample into two random groups (if nothing else can be done!);Failure to replicate False positive in the original study False negative in the second one Population specificity Population stratification;Considerations at the beginning Will you have enough power? Who are the controls? Unrelated or family-based? A subgroup vs another one (males vs females)? Prospective sequential sampling or retrospective convenience samples for cases? Remember you will be testing whether the cases and controls are from the same population. The answer shouldn’t be obvious at the beginning.;An example of power calculation;An example of power calculation;Beware of the following flaws and fallacies of epidemiologic studies confounders (known or unknown) selection bias response bias misclassification bias variable observer Hawthorne effect (changes caused by the observer in the observed values) diagnostic accuracy bias regression to the mean significance Turkey nerd of nonsignificance cohort effect ecologic fallacy Berkson bias (selection bias in hospital-based studies) SEE: /epi/bc.html ;Categorical Data Analysis * 2x2 Table Analysis for Association Chi-squared (Pearson, Yates) Fisher G-test McNemars test: TDT, HRR (Logistic Regression) * Odds R