950
Views
12
CrossRef citations to date
0
Altmetric
TRENDS IN MOLECULAR MEDICINE

Planning a genome-wide association study: Points to consider

&
Pages 451-460 | Received 01 Jun 2010, Accepted 09 Mar 2011, Published online: 19 May 2011

References

  • Clayton DG. Prediction and interaction in complex disease genetics: experience in type 1 diabetes. PLoS Genet. 2009;5: e1000540.
  • Rich SS. Mapping genes in diabetes. Genetic epidemiological perspective. Diabetes. 1990;39:1315–9.
  • Redondo MJ, Yu L, Hawa M, Mackenzie T, Pyke DA, Eisenbarth GS, . Heterogeneity of type I diabetes: analysis of monozygotic twins in Great Britain and the United States. Diabetologia. 2001;44:354–62.
  • Lohmueller KE, Pearce CL, Pike M, Lander ES, Hirschhorn JN. Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. Nat Genet. 2003;33:177–82.
  • Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, . The sequence of the human genome. Science. 2001;291:1304–51.
  • Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, . Initial sequencing and analysis of the human genome. Nature. 2001;409:860–921.
  • International HapMap Consortium. The International HapMap Project. Nature. 2003;426:789–96.
  • International HapMap Consortium. A haplotype map of the human genome. Nature. 2005;437:1299–320.
  • Steemers FJ, Chang W, Lee G, Barker DL, Shen R, Gunderson KL. Whole-genome genotyping with the single-base extension assay. Nat Methods. 2006;3:31–3.
  • Li Y, Willer C, Sanna S, Abecasis G. Genotype imputation. Annu Rev Genomics Hum Genet. 2009;10:387–406.
  • Wang K, Zhang H, Ma D, Bucan M, Glessner JT, Abrahams BS, . Common genetic variants on 5p14.1 associate with autism spectrum disorders. Nature. 2009;459: 528–33.
  • Moffatt MF, Kabesch M, Liang L, Dixon AL, Strachan D, Heath S, . Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature. 2007;448:470–3.
  • Sleiman PM, Flory J, Imielinski M, Bradfield JP, Annaiah K, Willis-Owen SA, . Variants of DENND1B associated with asthma in children. N Engl J Med. 2010;362:36–44.
  • Zanke BW, Greenwood CM, Rangrej J, Kustra R, Tenesa A, Farrington SM, . Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24. Nat Genet. 2007;39:989–94.
  • Yeager M, Orr N, Hayes RB, Jacobs KB, Kraft P, Wacholder S, . Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. Nat Genet. 2007; 39:645–9.
  • Haiman CA, Patterson N, Freedman ML, Myers SR, Pike MC, Waliszewska A, . Multiple regions within 8q24 independently affect risk for prostate cancer. Nat Genet. 2007;39:638–44.
  • Freathy RM, Mook-Kanamori DO, Sovio U, Prokopenko I, Timpson NJ, Berry DJ, . Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight. Nat Genet. 2010;42:430–5.
  • Barrett JC, Hansoul S, Nicolae DL, Cho JH, Duerr RH, Rioux JD, . Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. Nat Genet. 2008;40:955–62.
  • Fisher SA, Tremelling M, Anderson CA, Gwilliam R, Bumpstead S, Prescott NJ, . Genetic determinants of ulcerative colitis include the ECM1 locus and five loci implicated in Crohn's disease. Nat Genet. 2008;40:710–2.
  • Hampe J, Franke A, Rosenstiel P, Till A, Teuber M, Huse K, . A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat Genet. 2007;39:207–11.
  • Imielinski M, Baldassano RN, Griffiths A, Russell RK, Annese V, Dubinsky M, . Common variants at five new loci associated with early-onset inflammatory bowel disease. Nat Genet. 2009;41:1335–40.
  • Kugathasan S, Baldassano RN, Bradfield JP, Sleiman PM, Imielinski M, Guthery SL, . Loci on 20q13 and 21q22 are associated with pediatric-onset inflammatory bowel disease. Nat Genet. 2008;40:1211–5.
  • Parkes M, Barrett JC, Prescott NJ, Tremelling M, Anderson CA, Fisher SA, . Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility. Nat Genet. 2007;39: 830–2.
  • Rioux JD, Xavier RJ, Taylor KD, Silverberg MS, Goyette P, Huett A, . Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet. 2007;39:596–604.
  • Todd JA, Walker NM, Cooper JD, Smyth DJ, Downes K, Plagnol V, . Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. Nat Genet. 2007;39:857–64.
  • Hakonarson H, Grant SFA, Bradfield JP, Marchand L, Kim CE, Glessner JT, . A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene. Nature. 2007;448:591–4.
  • Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007;447:661–78.
  • Sladek R, Rocheleau G, Rung J, Dina C, Shen L, Serre D, . A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature. 2007;445:881–5.
  • Saxena R, Voight BF, Lyssenko V, Burtt NP, de Bakker PI, Chen H, . Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science. 2007;316:1331–6.
  • Zeggini E, Weedon MN, Lindgren CM, Frayling TM, Elliott KS, Lango H, . Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science. 2007;316:1336–41.
  • Scott LJ, Mohlke KL, Bonnycastle LL, Willer CJ, Li Y, Duren WL, . A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science. 2007;316:1341–5.
  • Steinthorsdottir V, Thorleifsson G, Reynisdottir I, Benediktsson R, Jonsdottir T, Walters GB, . A variant in CDKAL1 influences insulin response and risk of type 2 diabetes. Nat Genet. 2007;39:770–5.
  • Zeggini E, Scott LJ, Saxena R, Voight BF, Marchini JL, Hu T, . Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat Genet. 2008;40:638–45.
  • Unoki H, Takahashi A, Kawaguchi T, Hara K, Horikoshi M, Andersen G, . SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations. Nat Genet. 2008;40:1098–102.
  • Yasuda K, Miyake K, Horikawa Y, Hara K, Osawa H, Furuta H, . Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus. Nat Genet. 2008; 40:1092–7.
  • Herbert A, Gerry NP, McQueen MB, Heid IM, Pfeufer A, Illig T, . A common genetic variant is associated with adult and childhood obesity. Science. 2006;312: 279–83.
  • Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, . A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007;316:889–94.
  • Loos RJ, Lindgren CM, Li S, Wheeler E, Zhao JH, Prokopenko I, . Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nat Genet. 2008; 40:768–75.
  • Thorleifsson G, Walters GB, Gudbjartsson DF, Steinthorsdottir V, Sulem P, Helgadottir A, . Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat Genet. 2009; 41:18–24.
  • Willer CJ, Speliotes EK, Loos RJ, Li S, Lindgren CM, Heid IM, . Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet. 2009;41:25–34.
  • Klein RJ, Zeiss C, Chew EY, Tsai JY, Sackler RS, Haynes C, . Complement factor H polymorphism in age-related macular degeneration. Science. 2005;308:385–9.
  • Helgadottir A, Thorleifsson G, Manolescu A, Gretarsdottir S, Blondal T, Jonasdottir A, . A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science. 2007;316:1491–3.
  • McPherson R, Pertsemlidis A, Kavaslar N, Stewart A, Roberts R, Cox DR, . A common allele on chromosome 9 associated with coronary heart disease. Science. 2007;316: 1488–91.
  • Easton DF, Pooley KA, Dunning AM, Pharoah PD, Thompson D, Ballinger DG, . Genome-wide association study identifies novel breast cancer susceptibility loci. Nature. 2007;447:1087–93.
  • Novembre J, Johnson T, Bryc K, Kutalik Z, Boyko AR, Auton A, . Genes mirror geography within Europe. Nature. 2008;456:98–101.
  • Devlin B, Roeder K. Genomic control for association studies. Biometrics. 1999;55:997–1004.
  • Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D. Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet. 2006;38:904–9.
  • Grant SF, Thorleifsson G, Reynisdottir I, Benediktsson R, Manolescu A, Sainz J, . Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet. 2006;38:320–3.
  • Helgason A, Palsson S, Thorleifsson G, Grant SF, Emilsson V, Gunnarsdottir S, . Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution. Nat Genet. 2007;39:218–25.
  • Zeggini E, McCarthy MI. TCF7L2: the biggest story in diabetes genetics since HLA? Diabetologia. 2007;50:1–4.
  • Richards JB, Rivadeneira F, Inouye M, Pastinen TM, Soranzo N, Wilson SG, . Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study. Lancet. 2008;371:1505–12.
  • Styrkarsdottir U, Halldorsson BV, Gretarsdottir S, Gudbjartsson DF, Walters GB, Ingvarsson T, . Multiple genetic loci for bone mineral density and fractures. N Engl J Med. 2008;358:2355–65.
  • Styrkarsdottir U, Halldorsson BV, Gretarsdottir S, Gudbjartsson DF, Walters GB, Ingvarsson T, . New sequence variants associated with bone mineral density. Nat Genet. 2009;41:15–17.
  • Rivadeneira F, Styrkarsdottir U, Estrada K, Halldorsson BV, Hsu YH, Richards JB, . Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies. Nat Genet. 2009;41: 1199–206.
  • Hakonarson H, Grant SF, Bradfield JP, Marchand L, Kim CE, Glessner JT, . A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene. Nature. 2007;448:591–4.
  • Hakonarson H, Qu HQ, Bradfield JP, Marchand L, Kim CE, Glessner JT, . A novel susceptibility locus for type 1 diabetes on Chr12q13 identified by a genome-wide association study. Diabetes. 2008;57:1143–6.
  • Cooper JD, Smyth DJ, Smiles AM, Plagnol V, Walker NM, Allen JE, . Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci. Nat Genet. 2008;40:1399–401.
  • Barrett JC, Clayton DG, Concannon P, Akolkar B, Cooper JD, Erlich HA, . Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat Genet. 2009;41:703–7.
  • Grant SF, Qu HQ, Bradfield JP, Marchand L, Kim CE, Glessner JT, . Follow-up analysis of genome-wide association data identifies novel loci for type 1 diabetes. Diabetes. 2009;58:290–5.
  • Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, . A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science. 2006;314:1461–3.
  • Grant SF, Li M, Bradfield JP, Kim CE, Annaiah K, Santa E, . Association analysis of the FTO gene with obesity in children of Caucasian and African ancestry reveals a common tagging SNP. PLoS ONE. 2008;3:e1746.
  • Hinney A, Nguyen TT, Scherag A, Friedel S, Bronner G, Muller TD, . Genome wide association (GWA) study for early onset extreme obesity supports the role of fat mass and obesity associated gene (FTO) variants. PLoS ONE. 2007;2:e1361.
  • Dina C, Meyre D, Gallina S, Durand E, Korner A, Jacobson P, . Variation in FTO contributes to childhood obesity and severe adult obesity. Nat Genet. 2007;39: 724–6.
  • Scuteri A, Sanna S, Chen WM, Uda M, Albai G, Strait J, . Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet. 2007;3:e115.
  • Freathy RM, Bennett AJ, Ring SM, Shields B, Groves CJ, Timpson NJ, . Type 2 diabetes risk alleles are associated with reduced size at birth. Diabetes. 2009;58:1428–33.
  • Zhao J, Li M, Bradfield JP, Wang K, Zhang H, Sleiman P, . Examination of type 2 diabetes loci implicates CDKAL1 as a birth weight gene. Diabetes. 2009;58: 2414–8.
  • Zhao J, Bradfield JP, Zhang H, Annaiah K, Wang K, Kim CE, . Examination of all type 2 diabetes GWAS loci reveals HHEX-IDE as a locus influencing pediatric BMI. Diabetes. 2010;59:751–5.
  • Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, . Finding the missing heritability of complex diseases. Nature. 2009;461:747–53.
  • Weedon MN, Lettre G, Freathy RM, Lindgren CM, Voight BF, Perry JR, . A common variant of HMGA2 is associated with adult and childhood height in the general population. Nat Genet. 2007;39:1245–1250.
  • Gudbjartsson DF, Walters GB, Thorleifsson G, Stefansson H, Halldorsson BV, Zusmanovich P, . Many sequence variants affecting diversity of adult human height. Nat Genet. 2008;40:609–15.
  • Lettre G, Jackson AU, Gieger C, Schumacher FR, Berndt SI, Sanna S, . Identification of ten loci associated with height highlights new biological pathways in human growth. Nat Genet. 2008;40:584–91.
  • Sanna S, Jackson AU, Nagaraja R, Willer CJ, Chen WM, Bonnycastle LL, . Common variants in the GDF5-UQCC region are associated with variation in human height. Nat Genet. 2008;40:198–203.
  • Weedon MN, Lango H, Lindgren CM, Wallace C, Evans DM, Mangino M, . Genome-wide association analysis identifies 20 loci that influence adult height. Nat Genet. 2008;40:575–83.
  • Lango Allen H, Estrada K, Lettre G, Berndt SI, Weedon MN, Rivadeneira F, . Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature. 2010;467:832–8.
  • Dickson SP, Wang K, Krantz I, Hakonarson H, Goldstein DB. Rare variants create synthetic genome-wide associations. PLoS Biol. 2010;8:e1000294.
  • Wang K, Dickson SP, Stolle CA, Krantz ID, Goldstein DB, Hakonarson H. Interpretation of association signals and identification of causal variants from genome-wide association studies. Am J Hum Genet. 2010;86:730–42.
  • McCarthy MI, Abecasis GR, Cardon LR, Goldstein DB, Little J, Ioannidis JP, . Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nat Rev Genet. 2008;9:356–69.
  • Manolio TA, Brooks LD, Collins FS. A HapMap harvest of insights into the genetics of common disease. J Clin Invest. 2008;118:1590–605.
  • Altshuler D, Daly MJ, Lander ES. Genetic mapping in human disease. Science. 2008;322:881–8.
  • Gerken T, Girard CA, Tung YC, Webby CJ, Saudek V, Hewitson KS, . The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science. 2007;318:1469–72.
  • Fischer J, Koch L, Emmerling C, Vierkotten J, Peters T, Bruning JC, . Inactivation of the Fto gene protects from obesity. Nature. 2009;458:894–8.
  • Hafler DA, Compston A, Sawcer S, Lander ES, Daly MJ, De Jager PL, . Risk alleles for multiple sclerosis identified by a genomewide study. N Engl J Med. 2007;357:851–62.
  • Bottini N, Vang T, Cucca F, Mustelin T. Role of PTPN22 in type 1 diabetes and other autoimmune diseases. Semin Immunol. 2006;18:207–13.
  • Wang K, Baldassano R, Zhang H, Qu HQ, Imielinski M, Kugathasan S, . Comparative genetic analysis of inflammatory bowel disease and type 1 diabetes implicates multiple loci with opposite effects. Hum Mol Genet. 2010; 19:2059–67.
  • Yochum GS, McWeeney S, Rajaraman V, Cleland R, Peters S, Goodman RH. Serial analysis of chromatin occupancy identifies beta-catenin target genes in colorectal carcinoma cells. Proc Natl Acad Sci USA. 2007; 104: 3324–9.
  • Duval A, Busson-Leconiat M, Berger R, Hamelin R. Assignment of the TCF-4 gene (TCF7L2) to human chromosome band 10q25.3. Cytogenet Cell Genet. 2000;88: 264–5.
  • Pomerantz MM, Ahmadiyeh N, Jia L, Herman P, Verzi MP, Doddapaneni H, . The 8q24 cancer risk variant rs6983267 shows long-range interaction with MYC in colorectal cancer. Nat Genet. 2009;41:882–4.
  • Tuupanen S, Turunen M, Lehtonen R, Hallikas O, Vanharanta S, Kivioja T, . The common colorectal cancer predisposition SNP rs6983267 at chromosome 8q24 confers potential to enhanced Wnt signaling. Nat Genet. 2009;41:885–90.
  • Frayling TM, Colhoun H, Florez JC. A genetic link between type 2 diabetes and prostate cancer. Diabetologia. 2008;51: 1757–60.
  • Schernthaner G, Hink S, Kopp HP, Muzyka B, Streit G, Kroiss A. Progress in the characterization of slowly progressive autoimmune diabetes in adult patients (LADA or type 1.5 diabetes). Exp Clin Endocrinol Diabetes. 2001;109 Suppl 2:S94–108.
  • Qu HQ, Grant SF, Bradfield JP, Kim C, Frackelton E, Hakonarson H, . Association analysis of type 2 diabetes Loci in type 1 diabetes. Diabetes. 2008;57: 1983–6.
  • Huxtable SJ, Saker PJ, Haddad L, Walker M, Frayling TM, Levy JC, . Analysis of parent-offspring trios provides evidence for linkage and association between the insulin gene and type 2 diabetes mediated exclusively through paternally transmitted class III variable number tandem repeat alleles. Diabetes. 2000;49:126–30.
  • Qu HQ, Polychronakos C. The TCF7L2 locus and type 1 diabetes. BMC Med Genet. 2007;8:51.
  • Field SF, Howson JM, Smyth DJ, Walker NM, Dunger DB, Todd JA. Analysis of the type 2 diabetes gene, TCF7L2, in 13,795 type 1 diabetes cases and control subjects. Diabetologia. 2007;50:212–3.
  • Cervin C, Lyssenko V, Bakhtadze E, Lindholm E, Nilsson P, Tuomi T, . Genetic similarities between latent autoimmune diabetes in adults, type 1 diabetes, and type 2 diabetes. Diabetes. 2008;57:1433–7.
  • Szepietowska B, Moczulski D, Wawrusiewicz-Kurylonek N, Grzeszczak W, Gorska M, Szelachowska M. Transcription factor 7-like 2-gene polymorphism is related to fasting C peptide in latent autoimmune diabetes in adults (LADA). Acta Diabetol. 2010;47:83–6.
  • Samani NJ, Erdmann J, Hall AS, Hengstenberg C, Mangino M, Mayer B, . Genomewide association analysis of coronary artery disease. N Engl J Med. 2007;357:443–53.
  • Wei Z, Wang K, Qu HQ, Zhang H, Bradfield J, Kim C, . From disease association to risk assessment: an optimistic view from genome-wide association studies on type 1 diabetes. PLoS Genet. 2009;5:e1000678.
  • Wang K, Zhang H, Kugathasan S, Annese V, Bradfield JP, Russell RK, . Diverse genome-wide association studies associate the IL12/IL23 pathway with Crohn Disease. Am J Hum Genet. 2009;84:399–405.
  • Reich D, Patterson N, De Jager PL, McDonald GJ, Waliszewska A, Tandon A, . A whole-genome admixture scan finds a candidate locus for multiple sclerosis susceptibility. Nat Genet. 2005;37:1113–8.
  • Gunderson KL, Steemers FJ, Lee G, Mendoza LG, Chee MS. A genome-wide scalable SNP genotyping assay using microarray technology. Nat Genet. 2005;37:549–54.
  • Sebat J, Lakshmi B, Malhotra D, Troge J, Lese-Martin C, Walsh T, . Strong association of de novo copy number mutations with autism. Science. 2007;316:445–9.
  • Marshall CR, Noor A, Vincent JB, Lionel AC, Feuk L, Skaug J, . Structural variation of chromosomes in autism spectrum disorder. Am J Hum Genet. 2008;82:477–88.
  • Weiss LA, Shen Y, Korn JM, Arking DE, Miller DT, Fossdal R, . Association between microdeletion and microduplication at 16p11.2 and autism. N Engl J Med. 2008;358: 667–75.
  • Glessner JT, Wang K, Cai G, Korvatska O, Kim CE, Wood S, . Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. Nature. 2009;459:569–73.
  • Elia J, Gai X, Xie HM, Perin JC, Geiger E, Glessner JT, . Rare structural variants found in attention-deficit hyperactivity disorder are preferentially associated with neurodevelopmental genes. Mol Psychiatry. 2010;15:637–46.
  • Stefansson H, Rujescu D, Cichon S, Pietilainen OP, Ingason A, Steinberg S, . Large recurrent microdeletions associated with schizophrenia. Nature. 2008;455:232–6.
  • Walsh T, McClellan JM, McCarthy SE, Addington AM, Pierce SB, Cooper GM, . Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science. 2008;320:539–43.
  • Glessner JT, Reilly MP, Kim CE, Takahashi N, Albano A, Hou C, . Strong synaptic transmission impact by copy number variations in schizophrenia. Proc Natl Acad Sci U S A. 2010;107:10584–9.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.