BIOSTAT graduate level using R and plink

2. [65 points] Genome-Wide Association Study (GWAS) of Dichotomous Transferrin Serum Iron is essential for a number of biochemical functions including oxygen transport and oxidative phosphorylation. Excessive iron can cause various disorders, such as iron-overload-related liver diseases, whereas iron de ciency can lead to anemia. Iron status can be assessed by measuring the levels of serum transferrin in the blood. Transferrin is a beta globulin in blood plasma capable of combining with ferric ions and is essential for transporting iron in the body. A 2009 American Journal of Human Genetics article entitled \Variants in TF and HFE Explain 40% of Genetic Variation in Serum-Transferrin Levels Genome" by Benyamin et al. performed a GWAS of transferrin, and a link to this paper has been provided for you. You will conduct a GWAS of transferring for case-control phenotype of Transfer- rin using the PLINK le provided to your for Lecture 20 and write a report about your analysis and results. The PLINK les \Transferrin.bed", \Transferrin.fam", and \Transferrin.bim" contain genome-screen data for a sample of individuals with Eu- ropean ancestry. The phenotype le \TrBinaryPheno.txt" contains a dichotomized transferrin variable where individuals who individuals with "high" transferrin mea- surements were identi ed to be cases, with a value of 2 for the dichotomous variable, and the controls are individuals who do not have "high" transferrin measurements, and have a value of 1 for this variable. Individuals with missing transferrin measure- ments have a value of 0 for the dichotomous transferrin phenotype. The report is to be between 5 and 10 double spaced pages, including any tables and gures. The report should include the following sections and adhere to the guidelines given below for each section: (a) Title: The title of the report may occupy no more than three lines of type. Each line should contain no more than 54 characters, including spaces. The title should convey the conceptual signi cance of the report to a broad readership. (b) Introduction: The Introduction should be succinct, with no subheadings, and should present the background information necessary to provide a biological context for the results. (c) Material and Methods: The Material and Methods section needs to include sucient detail so that readers can understand how the experiments were per- formed, and so that all procedures can be repeated, in conjunction with cited references. This section should also include a description of the data, the hy- potheses of interest, and the statistical methods employed in the study to analyze the data. (d) Results: The Results section should include the results of your analysis and should highlight any signi cant ndings. If there are SNPs that have a signif- icant association with the dichotomous transferrin phenotype, you should also determine if these SNPs are in genes. (e) Discussion: The Discussion section should explain the signi cance of the results and place them into a broader context. It should not be redundant with the Results section. Include in the discussion a brief description of the Benyamin et al. (2009) and a comparison of your association results to the transferrin GWAS results from this article.

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