Yeager, M., et al. [(2007) Nature Genetics 39:645–649] and Sladek, R., et al. [(2007) Nature 445:881–885] have used single-nucleotide polymorphisms (SNPs) in genome-wide association studies (GWAS) to identify novel risk loci for prostate cancer and Type 2 diabetes, respectively. Each study suggests that disease-risk genes can be identified that significantly contribute to the disease state. Given your understanding of such complex diseases, what would you determine as reasonable factors to consider when interpreting the results of GWAS?

Key Concepts

Single-Nucleotide Polymorphisms (SNPs)

Single-nucleotide polymorphisms (SNPs) are the most common type of genetic variation among people, where a single nucleotide in the genome is altered. These variations can influence how individuals respond to diseases, medications, and environmental factors. In genome-wide association studies (GWAS), SNPs are used as markers to identify genetic loci associated with complex diseases, helping researchers pinpoint potential risk factors.

Genome-Wide Association Studies (GWAS)

Genome-wide association studies (GWAS) are research methods used to identify genetic variants associated with specific diseases by scanning the genomes of many individuals. By comparing the frequency of SNPs in affected versus unaffected individuals, researchers can identify loci that may contribute to disease risk. GWAS have been instrumental in uncovering genetic factors for complex diseases like prostate cancer and Type 2 diabetes.

Complex Diseases

Complex diseases, such as prostate cancer and Type 2 diabetes, are influenced by multiple genetic and environmental factors rather than a single gene mutation. These diseases often exhibit polygenic inheritance, where many genes contribute to the risk and severity of the condition. Understanding the multifactorial nature of these diseases is crucial when interpreting GWAS results, as it highlights the need to consider gene-environment interactions and the cumulative effect of multiple risk alleles.