Exploring the unknown: Assumptions about allelic architecture and strategies for susceptibility variant discovery

Genome Medicine

Volumn 1, Issue 7, 2009, Pages

  McCarthy, Mark I ^a,b  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ALLELE; GENE FREQUENCY; GENE IDENTIFICATION; GENE LOCUS; GENE NUMBER; GENE SEQUENCE; GENE STRUCTURE; GENETIC ASSOCIATION; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; GENOME ANALYSIS; HERITABILITY; HUMAN; PHENOTYPE; PRIORITY JOURNAL; SHORT SURVEY; SIGNAL TRANSDUCTION;

EID: 70350038689     PISSN: None     EISSN: 1756994X     Source Type: Journal    
DOI: 10.1186/gm66     Document Type: Short Survey

References (24)

1. McCarthy MI, Abecasis GR, Cardon LR, Goldstein DB, Little J, Ioannidis JP, Hirschhorn JN: Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nat Rev Genet 2008, 9:356-369.
2. Hindorff LA, Sethupathy P, Junkins HA, Ramos EM, Mehta JP, Collins FS, Manolio TA: Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci USA 2009, 106:9362-9367.
3. OPG: a Catalog of Published Genome-Wide Association Studies [http://www.genome.gov/gwastudies]
4. Cadwell K, Liu JY, Brown SL, Miyoshi H, Loh J, Lennerz JK, Kishi C, Kc W, Carrero JA, Hunt S, Stone CD, Brunt EM, Xavier RJ, Sleckman BP, Li E, Mizushima N, Stappenbeck TS, Virgin HW 4th: A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells. Nature 2008, 456:259-263.
5. Glessner JT, Wang K, Cai G, Korvatska O, Kim CE, Wood S, Zhang H, Estes A, Brune CW, Bradfield JP, Imielinski M, Frackelton EC, Reichert J, Crawford EL, Munson J, Sleiman PM, Chiavacci R, Annaiah K, Thomas K, Hou C, Glaberson W, Flory J, Otieno F, Garris M, Soorya L, Klei L, Piven J, Meyer KJ, Anagnostou E, Sakurai T, et al.: Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. Nature 2009, 459:569-573.
6. Wang K, Zhang H, Ma D, Bucan M, Glessner JT, Abrahams BS, Salyakina D, Imielinski M, Bradfield JP, Sleiman PM, Kim CE, Hou C, Frackelton E, Chiavacci R, Takahashi N, Sakurai T, Rappaport E, Lajonchere CM, Munson J, Estes A, Korvatska O, Piven J, Sonnenblick LI, Alvarez Retuerto AI, Herman EI, Dong H, Hutman T, Sigman M, Ozonoff S, Klin A, et al.:Common genetic variants on 5p14.1 associate with autism spectrum disorders. Nature 2009, 459:528-533.
7. Maher B: Personal genomes: the case of the missing heritability. Nature 2008, 456:18-21.
8. Gol dstein DB: Common genetic variation and human traits. N Engl J Med 2009, 360:1696-1698.
9. Hirschhorn JN: Genome-wide association studies - illuminating biologic pathways. N Engl J Med 2009, 360:1699-1701.
10. Visscher PM, Hill WG, Wray NR: Heritability in the genomics era - concepts and misconceptions. Nat Rev Genet 2008, 9:255-266.
11. Hill WG, Goddard ME, Visscher PM: Data and theory point to mainly additive genetic variance for complex traits. PLoS Genet 2008, 4:e1000008.
12. Doris PA: Hypertension genetics, single nucleotide polymorphisms, and the common disease: common variant hypothesis. Hypertension 2002, 39:323-331.
13. Weedon MN, Lango H, Lindgren CM, Wallace C, Evans DM, Mangino M, Freathy RM, Perry JR, Stevens S, Hall AS, Samani NJ, Shields B, Prokopenko I, Farrall M, Dominiczak A; Diabetes Genetics Initiative; Wellcome Trust Case Control Consortium, Johnson T, Bergmann S, Beckmann JS, Vollenweider P, Waterworth DM, Mooser V, Palmer CN, Morris AD, Ouwehand WH; Cambridge GEM Consortium, Zhao JH, Li S, Loos RJ, et al.: Genome-wide association analysis identifies 20 loci that influence adult height. Nat Genet 2008, 40:575-583.
14. Loos RJF, Lindgren CM, Li S, Wheeler E, Zhao JH, Prokopenko I, Inouye M, Freathy RM, Attwood AP, Beckmann JS, Berndt SI, The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, Bergmann S, Bennett AJ, Bingham SA, Bochud M, Brown M, Cauchi S, Connell JM, Cooper C, Davey Smith G, Day I, Dina C, De S, Dermitzakis ET, Doney ASD, Elliott KS, Elliott P, Evans DM, Farooqi IS, et al.: Association studies involving over 90,000 people demonstrate that common variants near to MC4R influence fat mass, weight and risk of obesity. Nat Genet 2008, 40:768-775.
15. Bodmer W, Bonilla C: Common and rare variants in multifactorial susceptibility to common diseases. Nat Genet 2008, 40:695-701.
16. Schork NJ, Murray SS, Frazer KA, Topol EJ: Common vs. rare allele hypotheses for complex diseases. Curr Opin Genet Dev 2009, 19:212-219.
17. International Schizophrenia Consortium: Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature 2008, 455:237-241.
18. Stefansson H, Rujescu D, Cichon S, Pietiläinen OP, Ingason A, Steinberg S, Fossdal R, Sigurdsson E, Sigmundsson T, Buizer-Voskamp JE, Hansen T, Jakobsen KD, Muglia P, Francks C, Matthews PM, Gylfason A, Halldorsson BV, Gudbjartsson D, Thorgeirsson TE, Sigurdsson A, Jonasdottir A, Jonasdottir A, Bjornsson A, Mattiasdottir S, Blondal T, Haraldsson M, Magnusdottir BB, Giegling I, Möller HJ, Hartmann A, et al.: Large recurrent microdeletions associated with schizophrenia. Nature 2008, 455:232-236.
19. Barrett JC, Clayton DG, Concannon P, Akolkar B, Cooper JD, Erlich HA, Julier C, Morahan G, Nerup J, Nierras C, Plagnol V, Pociot F, Schuilenburg H, Smyth DJ, Stevens H, Todd JA, Walker NM, Rich SS; The Type 1 Diabetes Genetics Consortium: Genome-wide association study and metaanalysis find that over 40 loci affect risk of type 1 diabetes. Nat Genet 2009, doi:10.1038/ng.381.
20. Russell RK, Nimmo ER, Satsangi J: Molecular genetics of Crohn's disease. Curr Opin Genet Dev 2004, 14:264-270.
21. Ng MC, Park KS, Oh B, Tam CH, Cho YM, Shin HD, Lam VK, Ma RC, So WY, Cho YS, Kim HL, Lee HK, Chan JC, Cho NH: Implication of genetic variants near TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, and FTO in type 2 diabetes and obesity in 6,719 Asians. Diabetes 2008, 57: 2226-2233.
22. Nejentsev S, Walker N, Riches D, Egholm M, Todd JA: Rare variants of IFIH1, a gene implicated in antiviral responses, protect against type 1 diabetes. Science 2009, 324:387-389.
23. McCarthy MI, Hattersley AT: Learning from molecular genetics: novel insights arising from the definition of genes for monogenic and type 2 diabetes. Diabetes 2008, 57:2889-2898.
24. Ghoussaini M, Song H, Koessler T, Al Olama AA, Kote-Jarai Z, Driver KE, Pooley KA, Ramus SJ, Kjaer SK, Hogdall E, DiCioccio RA, Whittemore AS, Gayther SA, Giles GG, Guy M, Edwards SM, Morrison J, Donovan JL, Hamdy FC, Dearnaley DP, Ardern-Jones AT, Hall AL, O'Brien LT, Gehr-Swain BN, Wilkinson RA, Brown PM, Hopper JL, Neal DE, Pharoah PD, Ponder BA, et al.: Multiple loci with different cancer specificities within the 8q24 gene desert. J Natl Cancer Inst 2008, 100: 962-966.