It is now established that some of the most common human diseases, such as hypertension, diabetes, mental disorders, and asthma, have a polygenic basis, with multiple genetic loci contributing small independent effects, resulting in a disease phenotype. Conventional linkage analyses lack the statistical power to detect such genetic variants. In GWASs, large cohorts of patients with and without a disease (rather than families) are examined across the entire genome for variant SNPs that are overrepresented in persons with the disease. This identifies regions of the genome that contain a variant gene or genes that confer disease susceptibility. The causal variant within the region is then provisionally identified using a “candidate gene” approach, in which genes are selected based on how tightly they are associated with the disease and whether their biologic function seems likely to be involved in the disease under study. In addition to polygenic diseases, GWASs also have led to the identification of genetic loci that modulate common quantitative traits in humans, such as height, body mass, hair and eye color, and bone density.
We end this chapter to reflect on the current genomic era of medicine. Advances in understanding the molecular basis of human disease are taking place at a breathtaking pace, as are molecular diagnostic techniques. Throughout this book we will illustrate how these changes have impacted on the management of certain diseases in the clinic. By the time this book reaches the reader we hope that many more such examples will become commonplace.
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