Common disease-common variant

Common Disease-Common Variant (CDCV) hypothesis posits that common diseases are attributable in part to allelic variants present in a significant fraction of the population. This hypothesis contrasts with the Common Disease-Rare Variant (CDRV) hypothesis, which suggests that rare mutations with large effects are responsible for a significant proportion of the genetic contribution to common diseases. The CDCV hypothesis has significant implications for the study of genetics, genomic medicine, and the development of therapeutic interventions.

Overview

The CDCV hypothesis emerged from observations in population genetics and the study of complex diseases. It suggests that the genetic architecture of many common diseases, such as type 2 diabetes, coronary artery disease, and asthma, is influenced by a relatively small number of alleles that are common in the population. These alleles individually confer a small to moderate increase in disease risk but can have a significant impact at the population level due to their high frequency.

Genetic Basis

Under the CDCV hypothesis, the alleles associated with disease susceptibility are common, with a minor allele frequency (MAF) of greater than 5%. These variants are often located in or near genes that play a critical role in disease pathophysiology. The identification of these variants typically relies on genome-wide association studies (GWAS), which scan the genome for single-nucleotide polymorphisms (SNPs) that occur more frequently in individuals with a particular disease compared to healthy controls.

Implications for Research and Medicine

The CDCV hypothesis has several important implications for biomedical research and the practice of medicine. It suggests that a significant portion of the genetic risk for common diseases can be captured through the study of common genetic variants. This has led to the prioritization of GWAS and the development of large-scale biobanks and genomic databases. Furthermore, understanding the genetic basis of disease according to the CDCV hypothesis can inform the development of targeted therapies and personalized medicine approaches.

Challenges and Criticisms

One of the main challenges in validating the CDCV hypothesis is the complex nature of genetic contributions to common diseases. Many diseases are influenced by a large number of genetic variants, each contributing a small amount to the overall risk, as well as by environmental factors and gene-environment interactions. Additionally, the effect sizes of common variants identified by GWAS are often small, making it difficult to translate these findings into clinical practice.

Future Directions

Research efforts continue to explore the validity and limitations of the CDCV hypothesis. This includes the integration of GWAS data with other genomic and biological data to better understand the functional impact of common variants. Additionally, there is an increasing focus on the role of polygenic risk scores, which aggregate the effects of many common variants to predict an individual's disease risk, in clinical settings.

See Also

• Genome-wide association study
• Polygenic risk score
• Population genetics
• Genomic medicine
• Single-nucleotide polymorphism