Common disease-common variant

Hypothesis for alleles

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 evolutionarily neutral in part because so many genes influence the traits. The hypothesis has held in the case of putative causal variants in apolipoprotein E, including APOE ε4, associated with Alzheimer's disease.[1] IL23R has been found to be associated with Crohn's disease; the at-risk allele has a frequency of 93% in the general population [citation needed].

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. Research has linked common SNPs to diseases such as type 2 diabetes, Alzheimer's, schizophrenia and hypertension.[2][3][4][5][6]

## See also

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* Rare functional variant

## References

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1. ^ 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
2. ^ Duerr, R. H.; Taylor, K. D.; Brant, S. R.; Rioux, J. D.; Silverberg, M. S.; Daly, M. J.; Steinhart, A. H.; Abraham, C.; Regueiro, M.; Griffiths, A.; Dassopoulos, T.; Bitton, A.; Yang, H.; Targan, S.; Datta, L. W.; Kistner, E. O.; Schumm, L. P.; Lee, A. T.; Gregersen, P. K.; Barmada, M. M.; Rotter, J. I.; Nicolae, D. L.; Cho, J. H. (2006). "A Genome-Wide Association Study Identifies IL23R as an Inflammatory Bowel Disease Gene". Science. 314 (5804): 1461–1463\. Bibcode:2006Sci...314.1461D. doi:10.1126/science.1135245. ISSN 0036-8075. PMC 4410764. PMID 17068223.
3. ^ Levy, Daniel; Ehret, Georg B; Rice, Kenneth; Verwoert, Germaine C; Launer, Lenore J; Dehghan, Abbas; Glazer, Nicole L; Morrison, Alanna C; Johnson, Andrew D; Aspelund, Thor; Aulchenko, Yurii; Lumley, Thomas; Köttgen, Anna; Vasan, Ramachandran S; Rivadeneira, Fernando; Eiriksdottir, Gudny; Guo, Xiuqing; Arking, Dan E; Mitchell, Gary F; Mattace-Raso, Francesco U S; Smith, Albert V; Taylor, Kent; Scharpf, Robert B; Hwang, Shih-Jen; Sijbrands, Eric J G; Bis, Joshua; Harris, Tamara B; Ganesh, Santhi K; O'Donnell, Christopher J; Hofman, Albert; Rotter, Jerome I; Coresh, Josef; Benjamin, Emelia J; Uitterlinden, André G; Heiss, Gerardo; Fox, Caroline S; Witteman, Jacqueline C M; Boerwinkle, Eric; Wang, Thomas J; Gudnason, Vilmundur; Larson, Martin G; Chakravarti, Aravinda; Psaty, Bruce M; van Duijn, Cornelia M (2009). "Genome-wide association study of blood pressure and hypertension". Nature Genetics. 41 (6): 677–687\. doi:10.1038/ng.384. ISSN 1061-4036. PMC 2998712. PMID 19430479.
4. ^ Storey, John D.; Raychaudhuri, Soumya; Plenge, Robert M.; Rossin, Elizabeth J.; Ng, Aylwin C. Y.; Purcell, Shaun M.; Sklar, Pamela; Scolnick, Edward M.; Xavier, Ramnik J.; Altshuler, David; Daly, Mark J. (2009). "Identifying Relationships among Genomic Disease Regions: Predicting Genes at Pathogenic SNP Associations and Rare Deletions". PLOS Genetics. 5 (6): e1000534. doi:10.1371/journal.pgen.1000534. ISSN 1553-7404. PMC 2694358. PMID 19557189.
5. ^ Seshadri, Sudha (2010). "Genome-wide Analysis of Genetic Loci Associated With Alzheimer Disease". JAMA. 303 (18): 1832–1840\. doi:10.1001/jama.2010.574. ISSN 0098-7484. PMC 2989531. PMID 20460622.
6. ^ Zeggini, Eleftheria; Scott, Laura J; Saxena, Richa; Voight, Benjamin F; Marchini, Jonathan L; Hu, Tianle; de Bakker, Paul IW; Abecasis, Gonçalo R; Almgren, Peter; Andersen, Gitte; Ardlie, Kristin; Boström, Kristina Bengtsson; Bergman, Richard N; Bonnycastle, Lori L; Borch-Johnsen, Knut; Burtt, Noël P; Chen, Hong; Chines, Peter S; Daly, Mark J; Deodhar, Parimal; Ding, Chia-Jen; Doney, Alex S F; Duren, William L; Elliott, Katherine S; Erdos, Michael R; Frayling, Timothy M; Freathy, Rachel M; Gianniny, Lauren; Grallert, Harald; Grarup, Niels; Groves, Christopher J; Guiducci, Candace; Hansen, Torben; Herder, Christian; Hitman, Graham A; Hughes, Thomas E; Isomaa, Bo; Jackson, Anne U; Jørgensen, Torben; Kong, Augustine; Kubalanza, Kari; Kuruvilla, Finny G; Kuusisto, Johanna; Langenberg, Claudia; Lango, Hana; Lauritzen, Torsten; Li, Yun; Lindgren, Cecilia M; Lyssenko, Valeriya; Marvelle, Amanda F; Meisinger, Christa; Midthjell, Kristian; Mohlke, Karen L; Morken, Mario A; Morris, Andrew D; Narisu, Narisu; Nilsson, Peter; Owen, Katharine R; Palmer, Colin NA; Payne, Felicity; Perry, John R B; Pettersen, Elin; Platou, Carl; Prokopenko, Inga; Qi, Lu; Qin, Li; Rayner, Nigel W; Rees, Matthew; Roix, Jeffrey J; Sandbæk, Anelli; Shields, Beverley; Sjögren, Marketa; Steinthorsdottir, Valgerdur; Stringham, Heather M; Swift, Amy J; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Timpson, Nicholas J; Tuomi, Tiinamaija; Tuomilehto, Jaakko; Walker, Mark; Watanabe, Richard M; Weedon, Michael N; Willer, Cristen J; Illig, Thomas; Hveem, Kristian; Hu, Frank B; Laakso, Markku; Stefansson, Kari; Pedersen, Oluf; Wareham, Nicholas J; Barroso, Inês; Hattersley, Andrew T; Collins, Francis S; Groop, Leif; McCarthy, Mark I; Boehnke, Michael; Altshuler, David (2008). "Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes". Nature Genetics. 40 (5): 638–645\. doi:10.1038/ng.120. ISSN 1061-4036. PMC 2672416. PMID 18372903.