Genomewide association studies

By 2006, genome-wide association scans had become a feasible approach to investigate the role of common sequence diversity in multifactorial diseases and traits. Reaching this position was the result of a number of different factors, notably the elucidation of the nature

Figure 9.8 Variation in recombination across chromosome 12. The recombination rate is plotted on the y axis, with genomic location along the x axis indicated by the ideogram of chromosome 12 banding shown below it. From Myers et al. (2005), reprinted with permission from AAAS.

and patterns of common nucleotide diversity within and between populations through the International HapMap Project, advances in genotyping technologies to allow accurate and affordable high throughput SNP typing at genome-wide coverage, and establishment of clearly phenotyped large sample collections for analysis (WTCCC 2007).

Genome-wide association studies are concerned with finding associations between common genetic variants and a particular trait by using a high density set of SNP markers to capture a substantial proportion of the common nucleotide diversity in the DNA samples analysed. The number of SNPs analysed is large, for example a minimum of 100 000 SNPs used in the initial scan is currently the threshold for the inclusion of a study in the catalogue of published genome-wide association studies maintained at the National Human Genome Research Institute (www.genome.gov/GWAstudies) (Hindorff et al. 2008). The approach has been very successful over a short space of time, with more than 50 disease susceptibility loci identified across a range of diseases - notably diabetes, inflammatory bowel disease (Section 9.5), and cancer, as well as coronary heart disease and asthma (McCarthy et al. 2008). Increasingly, the approach is also yielding major new insights into the genetic variation contributing to continuous traits ranging from height

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