In recent years, genomewide association studies (GWAS) have changed the game of identifying genetic bases for disease. These studies examine the entire genome for areas of genetic variation that may be associated with disease; so far, more than 600 such studies, looking at about 150 diseases and traits, have been published.
The latest article in the Genomic Medicine series, Genomewide Association Studies and Assessment of the Risk of Disease, by Dr. Teri Manolio, M.D., Ph.D., of the Office of Population Genomics at the National Human Genome Research Institute in Bethesda, MD, describes how these studies have been done, where they have proven useful, what challenges they have faced, and what potential they have for clinical relevance. An accompanying online interactive graphic illustrates various loci that the studies have implicated.
As the Manolio article explains, genomewide association studies have yielded both success stories and cautionary tales. Some studies have been valuable in implicating unlikely suspects of disease, such as complement H in age-related macular degeneration. Others have attempted to explain common conditions such as schizophrenia and failed, despite multiple searches, to identify significant genomic variants.
The article also addresses some of the key questions that have been raised by GWAS to date. For instance, why is it that the genetic variants identified, while abundant in number, still account for surprisingly little of the total heritability for the conditions being studied? If they only explain a small proportion of the total genetic risk, what accounts for the remainder? Additionally, what is the broader clinical significance of these studies? Technology has made genotyping more affordable and reliable, but the role in clinical practice of susceptibility variants discovered by GWAS is not yet clear. Will their future lie in predicting or screening for disease, informing drug choice and treatment methods, or something else entirely?