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Genome-Wide Association Study (GWAS)

(Modified on the Wikipedia article)


       Genome-wide association study is a novel and rapidly advancing approach in the field of molecular genetics that has led to exciting discoveries and hold great promises in delineating how our genomic information makes up what we are in health and sickness.  This practical introduction describes the concept of GWA study, its approach, methods, clinical applications, its limitations and its future trends.

What is Genome-wide association study?

       A genome-wide association study (GWAS), also known as whole genome association study (WGA study, or WGAS), is an examination of many common genetic variants in different individuals to see if any variant is associated with a trait. GWAS typically focus on associations between single-nucleotide polymorphisms (SNPs) and traits like major diseases.

       Any two human genomes differ in millions of different ways, ranging from variations in the individual nucleotides of the genomes (SNPs) to variations caused by deletions, insertions and copy number variations. Any of these may cause alterations in an individual's traits, or phenotype, which can be anything from disease risk to physical properties such as height. Prior to the introduction of GWA studies, the primary method of investigation was inheritance studies of genetic linkage in families. This approach had proven highly useful to identify single gene disorders. However, for common and complex diseases the results of genetic linkage studies proved hard to reproduce. The genetic association study was then developed as an alternative to linkage studies at detecting weak genetic effects.. The genetic association study asks if the allele of a genetic variant is found more often than expected in individuals with the phenotype of interest (e.g. with the disease being studied). 

       GWA studies normally compare the DNA of two groups of participants: people with the disease (cases) and similar people without (controls). Each person gives a sample of DNA, from which millions of genetic variants are read using SNP arrays. If one type of the variant (one allele) is more frequent in people with the disease, the SNP is said to be "associated" with the disease. The associated SNPs are then considered to mark a region of the human genome which influences the risk of disease. In contrast to methods which specifically test one or a few genetic regions, the GWA studies investigate the entire genome. GWA studies identify SNPs and other variants in DNA which are associated with a disease, but cannot on their own specify which genes are causal.

       The advent of biobanks, which are repositories of human biological material, the International HapMap Project which from 2003 had identified a large number of the common SNPs, and the  development of the methods to genotype all these SNPs using genotyping arrays greatly facilitate the development and progress of GWA studies.  are interrogated in a GWA study. GWA studies can focus on a subset of key SNPs that would describe most of the variation.

How are GWA studies actually conducted?

What are Clinical Applications of GWA study?

What are the Limitations of GWA studies?

What are The New Trends and Future?

Reference / Suggested Readings

Wikipedia: Genome-wide association study.  (Accessed: February 2013)

B. E. Stranger et al.: Progress and Promise of Genome-Wide Association Studies for Human Complex Trait Genetics.  Genetics 187 (2): 367-383, 2011.

Z. K. Stadle et al: Genome-Wide Association Studies of Cancer: Principles and Potential Utility. Oncology. 24 (7): 1-2, 2010.

W. G, Feero & A. E. Guttmacher: Genomewide Association Studies and Assessment of the Risk of Disease. N Engl J Med  363 (2):166-176, 2010.

J. Hardy & A. Singleton: Genomewide Association Studies and Human Disease. N Engl J Med 360 (17): 1759-1768, 2009.