Genetic Scoring Analysis: a way forward in Genome Wide Association Studies?

For the past 5 years genome-wide association studies(GWAS) have dominated the search for new genes forcomplex diseases overtaking other approaches of genefinding such as candidate gene and linkage analyses.Facilitated by technological developments in molecularbiology, genetic epidemiologists have so far discoveredmany variants associated with several common diseasesand traits such as Type 2 Diabetes, age-related maculardegeneration and Crohn’s disease [1]. There currently are26 established susceptibility genes published for type 2diabetes [2], 54 for human height and 22 for lipid levels [3,4]. These variants still explain only a small part of thegenetic variance or heritability, for human height and lipidsup to 4–6% [5, 6], and subsequently the search for novelvariants continues to unravel ‘missing heritability’.This missing heritability is explained by additional rarevariants with strong effects and/or common variants withweak effects, acting additively and/or interacting withother genetic and environmental variants. To discover theseadditional genetic factors, GWAS need to enlarge, and thishas led to further expansion of existing consortia and theestablishment of new ones. Since the first publication in2005 [7], GWAS have undergone enormous evolution:from 10,000 single nucleotide polymorphisms (SNPs) in100 individuals of a single sample [7] to 1 million geno-typed and