Whole genome association study: Tobacco consumption in the Cohorte Lausannoise
Background: The Cohorte Lausannoise (CoLaus) includes more than 6,000 individuals that have been extensively phenotyped for clinical observables related to cardiovascular risk factors and who have been genotyped for about half a million single nucleotide polymorphisms (SNPs).
Goal: The goal of the project is to perform a genome-wide association study that will potentially identify SNPs that are related to tobacco consumption and related phenotypes. Particular emphasis will be put on SNP tagging taste-specific genes such as the TAS2R.
Mathematical tools: The tool of choice for this project is logistic regression analysis. The student will learn the basics of regressing a given phenotype to a genotype and how this analysis is implemented on a computer to handle a large number of SNPs. If time permits the student will explore the effect of other phenotypes as covariables and/or environmental interactions.
Biological or Medical aspects: The “biology supervisor” will provide background of the medical significance of smoking in the general population and in the context of cardiovascular risks.
Supervisor: Pedro Marques-Vidal & Zoltan Kutalik
References: see Genome Wide Association Studies
Students: Anne Catherine Clerc & Zoe Enderlin
1st meeting: Fr. 27/2/09 with Murielle Bochud joint with students from the project Whole genome association study: Alcohol consumption in the Cohorte Lausannoise
- explain how Colaus data have been collected
- discuss which type of phenotypes should be use in the analyses (i.e. how new or corrected phenotypes can be they be constructed from the questionnaire data).
- documents to read:
1) paper by Firmann et al. describing the CoLaus study: Media: Firmann.pdf
2) the CoLaus questionnaire (to see how the phenotypic data was generated) Media: questColaus 1.pdf
3) the CoLaus codebook (to check names of the variables) Media: codage_des_variables.pdf
4) one paper in French describing the epidemiology of alcohol and tobacco Media: tabac_alcool.pdf
Students who have time are invited to visit lecture Media: GWAS_lecture.ppt by Sven Bergmann on Thu. 5/3/09 on GWAS in room AAB032 at the EPFL!
2nd meeting: Fr. 6/3/09 at 13:00 in Bugnon 27, DGM-328 (directions) with Sven Bergmann joint with students from the project Whole genome association study: Alcohol consumption in the Cohorte Lausannoise
- with all four students (2 for alcohol and 2 for tobacco GWAS).
- basics on regression and Genome Wide Association Studies (GWAS) methodology
- population stratification
3rd meeting: Fr. 13/3/09 at 12:15 in Bugnon 27, DGM-328 (directions) with Sven Bergmann joint with students from the project Whole genome association study: Tobacco consumption in the Cohorte Lausannoise
- with all four students (2 for alcohol and 2 for tobacco GWAS).
- principal component analysis and population stratification
- Further reading in preparation for Session 4: - Principal Component Analysis for gene-chip data, Reading in large text files with Matlab, Relatedness.
4th meeting: Fr. 20/3/09 at 13:20 in Bugnon 27, DGM-218 (directions) with Zoltán Kutalik joint with students from the project Whole genome association study: Alcohol consumption in the Cohorte Lausannoise
- "hands on": how to analyze large-scale GWAS data on a computer
- warm-up exercise with "semi-in-silico" data
5th meeting: Fr. 27/3/09 at 12:30 in Bugnon 27, DGM-218 (directions) with Zoltán Kutalik joint with students from the project Whole genome association study: Alcohol consumption in the Cohorte Lausannoise
- reading in large data sets (in plink format)
- detecting population stratification
6th meeting: Thu. 9/4/09 at 15:00 in Bugnon 27, DGM-218 (directions) with Zoltán Kutalik joint with students from the project Whole genome association study: Alcohol consumption in the Cohorte Lausannoise
- multiple testing corrections
- QQ-plots
7th meeting: Fri. 17/4/09 at 12:30 in Bugnon 27, DGM-218 (directions) with Zoltán Kutalik joint with students from the project Whole genome association study: Alcohol consumption in the Cohorte Lausannoise
- the tobacco related phenotypes
- CoLaus genotypes
(Project in Course: "Solving Biological Problems that require Math")
