Project Member
Jason Stein
The goal of this quarter
A project to detect how much of the variance of a disease must be rare alleles since it has not been already explained by previous association studies. Additionally, the possibility of how much information can be explained by genetics as currently implemented will be explored.
The Schedule for the quarter
Week 4: Setup the wiki page
Week 5: Explore the statistics and find previous literature on the topic
Week 6: Implement the statistics
Week 7: Find a disease and the associated heritability to test
Week 8: Find how much of the disease can be explained by rare alleles
Week 9: Make Presentation
Week 10: Project Presentation
Project Description
A project to detect how much of the variance of a disease must be rare alleles since it has not been already explained by previous association studies. Given a certain heritability of a disease, each significantly associated genetic locus explains a certain proportion of the disease risk up to the heritability for that disease. Since we have already searched the genome for most common diseases, and certain diseases have few (if any) loci that explain a large portion of the variance, it seems likely that there is a large proportion of rare alleles that are explaining the risk.
The goal of the project is to explore this point. That is we will assume that there is no epistasis between genes and that gene x environment factors are not a factor. With these assumptions, it should be possible to gain a probability of how many other rare alleles are necessary to explain the remaining amount of variance, and then how much more genotyping is required in order to have sufficient power to find these alleles.
Related Papers
- Reich and Lander, "On the Allelic Spectrum of Human Disease," Trends in Genetics, 2001 Link
- Hirschhorn and Daly, "Genome-Wide Association Studies for Common Diseases and Complex Traits," Nature Reviews Genetics, 2005 Link
- This paper gives a broad overview of the reason for using genome-wide association studies. It suggests that because individual alleles only explain small fractions of variance, fewer alleles are required to explain the heritability of common phenotypes if interactions between them are allowed.
- Rzhetsky, et al., "Probing Genetic Overlap Among Complex Human Phenotypes," PNAS, 2007 Link
- This paper does not measure genetic polymorphisms, but instead tries to understand how similar phenotypes are based on their age of onset and several other criteria. It shows that disorders like autism, bipolar disorder, and schizophrenia are highly related, and therefore probably share many genetic loci. This gives evidence that the spectrum of disease variation for these disorders may have similar common alleles.
- Iles, "What Can Genome-Wide Association Studies Tell Us about the Genetics of Common Disease?" PloS Genetics, 2008 Link
- This paper is basically what my project aims to do. The author is very critical of the common disease/common variant hypothesis that is the basis for the use of GWAS. There is some very interesting genome wide association modeling using the Encode region and inputting rare alleles.
April 20 2008
Spectrum of Disease Variation project begun.
April 21-27 2008
- What I did this week: Picked a topic and set up the wiki page
- What I'll do next week: Learn the statistics and find literature about the topic.
- How what you did compared to what you planned to do: Pretty well.
- What grade you think you deserve for your work on the project for the week: A+, since I did exactly what was asked.
April 28 - May 2 2008
- What I did this week: Studied for the midterm, and read a few papers.
- What I'll do next week: Read more papers and have some equations to explain what variance was described by a single SNP in a gene study.
- How what you did compared to what you planned to do: Could have done better, but you know the midterm was there.
- What grade you think you deserve for your work on the project for the week: I'd say you should take my grade on the midterm, and average it with a B and then go with that.
May 26 - May 30 2008
- What I did this week: Finished the project.
- What I'll do next week: Disney World
- What you did compared to what you planned to do: Success, project done.
- What grade do you think for your work on the project for the week: Quoth Eskin, "Yeah, that was a hard project". So I think that was a good sign.
