Genome-wide association studies (GWAS) have substantially improved our understanding

of the complex genetic architecture of many common traits. For

the last decade, more than a thousand genetic variants were discovered using

GWAS. The fast development of the field necessitated the improvement of existing

instruments as well as the development of new ones. This thesis discusses

methodology, software tools and new approaches facilitating the study of the

complex genetic architecture of common traits

Struchalin, M.V. (Maksim)

Erasmus University Digital Repository

STELLINGENBehorend bij het proefschriftAPPROACHES TO DISSECT THE COMPLEX GENETICARCHITECTURE OF COMMON TRAITS1. ProbABEL is an effective software tool for genome-wide associationstudies (this thesis).2. Prediction of height using genetic data is a powerful approach, howevercurrent prediction accuracy is low (this thesis).3. Variance heterogeneity analysis is currently the only method for detectinginteracting genetic variants involved in a complex model consisting ofmany interacting genetic and environmental factors (this thesis).4. Using collapsed genotypes in a genome-wide association study is morepowerful than single-variant analysis for detecting the presence of mul-tiple loss-of-function variants in the compound heterozygote state (thisthesis).5. A large part of the genetic component of total cholesterol is determinedby common variants with additive effects, however, multiple rare variantsplay a role in the extreme total cholesterol levels (this thesis).6. The genome-wide association study will probably remain an efficientway of investigating the remaining heritability (Teri A. Manolio 2009).7. A highly polygenic model of disease susceptibility with causal variantsacross the entire range of the allele-frequency spectrum contributes tocomplex-trait variation (Peter M. Visscher 2012).8. Dense genotyping and sequencing studies will facilitate discovering newgenetic variants associated with various traits.9. A sample of tens of millions of individuals is required to dissect thecomplex genetic architecture of many common traits.10. Future investments in genome-wide association studies are fully justifiedby the great potential to use the discovered genetic variants for predictionof traits and diseases even if the biological meaning of those variants willremain undiscovered.11. Similar to how genetic diversity is an important factor for the devel-opment of a species, the diversity of political, economical and culturalmodels is an important factor for the development of humanity.Maksim V Struchalin,22 mei 2013, Rotterdam

Approaches to Dissect the Complex Genetic Architecture of Common Traits

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