Epistasis Blog

From the Computational Genetics Laboratory at Dartmouth Medical School (www.epistasis.org)

Tuesday, August 30, 2005

IEEE Congress on Evolutionary Computing

We will be attending the 2005 IEEE Congress on Evolutionary Computing in Ednburgh, UK this week. We will present the following two papers:

White, B.C., Gilbert, J.C., Reif, D.M., Moore, J.H. A statistical comparison of grammatical evolution strategies in the domain of human genetics. Proceedings of the IEEE Congress on Evolutionary Computing, in press (2005).

White, B.C., Moore, J.H. A complete BNF grammar for systems biology thought experiments in human genetics using artificial life and biologically inspired computing. Proceedings of the IEEE Congress on Evolutionary Computing, in press (2005).

Monday, August 29, 2005

The role of epistatic gene interactions in the response to selection and the evolution of evolvability.

A new paper by Carter et al. in Theoretical Population Biology explores the role of epistasis in selection and evolvability with interesting results.

Carter AJ, Hermisson J, Hansen TF. The role of epistatic gene interactions in the response to selection and the evolution of evolvability. Theor Popul Biol. 2005 Aug 22 [PubMed]

Abstract:

It has been argued that the architecture of the genotype-phenotype map determines evolvability, but few studies have attempted to quantify these effects. In this article we use the multilinear epistatic model to study the effects of different forms of epistasis on the response to directional selection. We derive an analytical prediction for the change in the additive genetic variance, and use individual-based simulations to understand the dynamics of evolvability and the evolution of genetic architecture. This shows that the major determinant for the evolution of the additive variance, and thus the evolvability, is directional epistasis. Positive directional epistasis leads to an acceleration of evolvability, while negative directional epistasis leads to canalization. In contrast, pure non-directional epistasis has little effect on the response to selection. One consequence of this is that the classical epistatic variance components, which do not distinguish directional and non-directional effects, are useless as predictors of evolutionary dynamics. The build-up of linkage disequilibrium also has negligible effects. We argue that directional epistasis is likely to have major effects on evolutionary dynamics and should be the focus of empirical studies of epistasis.

Saturday, August 27, 2005

Atherosclerosis: from genetic polymorphisms to system genetics.

A new paper by Francois Cambien in Cardiovascular Toxicology reviews the importance of gene-gene and gene-environment interactions in atheroscerosis. A systems-genetics approach is discussed.

Cambien F, Tiret L. Atherosclerosis: from genetic polymorphisms to system genetics. Cardiovasc Toxicol. 2005;5(2):143-52. [PubMed]

Here is another nice review that covers the complexity of cardiovascular disease:

Sing CF, Stengard JH, Kardia SL. Dynamic relationships between the genome and exposures to environments as causes of common human diseases. World Rev Nutr Diet. 2004;93:77-91. [PubMed]

Monday, August 22, 2005

Classic paper on interactions

The following is a classic paper on the concept of interaction from an epidemiology and public health perspective. I highly recommend it for those new to the area. Rothman specifically discusses statistical vs. biological interaction.

Rothman KJ, Greenland S, Walker AM. Concepts of interaction. Am J Epidemiol. 1980 Oct;112(4):467-70. [PubMed]

Here is another one of my favorite papers by Dr. Rothman. Those of you that struggle with the appropriate correction for multiple testing should read this.

Rothman KJ. No adjustments are needed for multiple comparisons. Epidemiology. 1990 Jan;1(1):43-6. [PubMed]

Here is a new paper by Rothman that I have not read yet. Let me know how you like it.

Rothman KJ, Greenland S. Causation and causal inference in epidemiology. Am J Public Health. 2005 Jul;95 Suppl 1:S144-50. [PubMed]

Friday, August 19, 2005

Epistasis Is Coming. Are We Ready?

A editorial by Jonathan Rosand in the journal Stroke discusses epistasis and cites some of our work.

Rosand J. Epistasis Is Coming. Are We Ready? Stroke. 2005 Aug 11 [PubMed]

Friday, August 12, 2005

Epistasis in Autism detected using MDR

A new paper by Ma et al. in the American Journal of Human Genetics describes an interaction among GABA receptor subunit genes in Autism that was detected using our Multifactor Dimesnionality Reduction (MDR) method. More information on MDR can be found here. Our open-source MDR software package can be found here.

Ma DQ, Whitehead PL, Menold MM, Martin ER, Ashley-Koch AE, Mei H, Ritchie MD, Delong GR, Abramson RK, Wright HH, Cuccaro ML, Hussman JP, Gilbert JR, Pericak-Vance MA. Identification of Significant Association and Gene-Gene Interaction of GABA Receptor Subunit Genes in Autism. Am J Hum Genet. 2005 Sep;77(3):377-88. [PubMed]

Friday, August 05, 2005

Recent developments in genomewide association scans

A new paper by Thomas et al. reviews a meeting that was held in April to discuss genome-wide association analysis.

Thomas DC, Haile RW, Duggan D. Recent developments in genomewide association scans: a workshop summary and review. Am J Hum Genet. 2005 Sep;77(3):337-45. [PubMed]

Abstract:

With the imminent availability of ultra-high-volume genotyping platforms (on the order of 100,000-1,000,000 genotypes per sample) at a manageable cost, there is growing interest in the possibility of conducting genomewide association studies for a variety of diseases but, so far, little consensus on methods to design and analyze them. In April 2005, an international group of >100 investigators convened at the University of Southern California over the course of 2 days to compare notes on planned or ongoing studies and to debate alternative technologies, study designs, and statistical methods. This report summarizes these discussions in the context of the relevant literature. A broad consensus emerged that the time was now ripe for launching such studies, and several common themes were identified--most notably the considerable efficiency gains of multistage sampling design, specifically those made by testing only a portion of the subjects with a high-density genomewide technology, followed by testing additional subjects and/or additional SNPs at regions identified by this initial scan.

Detecting epistasis in genome-wide association studies will be a particularly difficult challenge. See our paper from last year on this topic:

Moore JH, Ritchie MD. The challenges of whole-genome approaches to common diseases. JAMA. 2004 Apr 7;291(13):1642-3. [PubMed]