Common disease-common variant
The common disease-common variant (often abbreviated CD-CV) hypothesis predicts that common disease-causing alleles, or variants, will be found in all human populations which manifest a given disease. Common variants (not necessarily disease-causing) are known to exist in coding and regulatory sequences of genes. According to the CD-CV hypothesis, some of those variants lead to susceptibility to complex polygenic diseases. Each variant at each gene influencing a complex disease will have a small additive or multiplicative effect on the disease phenotype. These diseases, or traits, are evolutionary neutral in part because so many genes influence the traits. The hypothesis has held true in the case of putative causal variants in apolipoprotein E, including APOE ε4, associated with Alzheimer's disease. IL23R has been found to be associated with Crohn's disease; the at-risk allele has a frequency 93% in the general population.
One common form of variation across human genomes is called a single nucleotide polymorphism (SNP). As indicated by the name, SNPs are single base changes in the DNA. SNP variants tend to be common in different human populations. These polymorphisms have been valuable as genomic signposts, or "markers," in the search for common variants that influence susceptibility to common diseases. Recently published research has linked common SNPs to diseases such as type 2 diabetes, Alzheimer's, schizophrenia and hypertension (Zeggini, 2008; Levy, 2009; Raychaudhuri, 2009; Seshadri, 2010)
- Expanded high-resolution genetic study of 109 Swedish families with Alzheimer's disease, Anna Sillén, Jorge Andrade, Lena Lilius, Charlotte Forsell, Karin Axelman, Jacob Odeberg, Bengt Winblad and Caroline Graff, European Journal of Human Genetics (2008) 16, 202–208; doi:10.1038/sj.ejhg.5201946; published online 24 October 2007
- Duerr, R.H. (2006) 'A Genome-Wide Association Study Identifies IL23R as an Inflammatory Bowel Disease Gene', Science. Vol. 314. pp. 1461 – 1463.
- Levy, D. (2009) 'Genome-wide association study of blood pressure and hypertension', Nature Genetics. Vol. 41. p.677-687.
- Raychaudhuri, S. (2009) 'Identifying Relationships among Genomic Disease Regions: Predicting Genes at Pathogenic SNP Associations and Rare Deletions', PLoS Genetics. Vol. 5(6).
- Seshadri, S. (2010) 'Genome-wide Analysis of Genetic Loci Associated With Alzheimer Disease', JAMA. Vol. 303(18).
- Zeggini, E. (2008) 'Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes', Nature Genetics. Vol. 40. p.638-645.