Abstract
A cost-efficient way to increase power in a genetic association study is to pool controls from different sources. The genotyping effort can then be directed to large case series. The Nordic Control database, NordicDB, has been set up as a unique resource in the Nordic area and the data are available for authorized users through the web portal (http://www.nordicdb.org). The current version of NordicDB pools together high-density genome-wide SNP information from ∼5000 controls originating from Finnish, Swedish and Danish studies and shows country-specific allele frequencies for SNP markers. The genetic homogeneity of the samples was investigated using multidimensional scaling (MDS) analysis and pairwise allele frequency differences between the studies. The plot of the first two MDS components showed excellent resemblance to the geographical placement of the samples, with a clear NW–SE gradient. We advise researchers to assess the impact of population structure when incorporating NordicDB controls in association studies. This harmonized Nordic database presents a unique genome-wide resource for future genetic association studies in the Nordic countries.
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References
Wellcome Trust Case Control Consortium: Genome-wide association study of 14 000 cases of seven common diseases and 3000 shared controls. Nature 2007; 447: 661–678.
Wrensch M, Jenkins RB, Chang JS et al: Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility. Nat Genet 2009; 41: 905–908.
Zheng SL, Sun J, Wiklund F et al: Cumulative association of five genetic variants with prostate cancer. N Engl J Med 2008; 358: 910–919.
Einarsdöttir K, Humphreys K, Bonnard C et al: Linkage disequilibrium mapping of CHEK2: common variation and breast cancer risk. PLoS Med 2006; 3: e168.
Diabetes Genetics Initiative of Broad Institute of Harvard and MIT, Lund University, and Novartis Institutes of BioMedical Research Saxena R, Voight BF, Lyssenko V et al: Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 2007; 316: 1331–1336.
Jakkula E, Rehnström K, Varilo T et al: The genome-wide patterns of variation expose significant substructure in a founder population. Am J Hum Genet 2008; 83: 787–794.
Bilguvar K, Yasuno K, Niemelä M et al: Susceptibility loci for intracranial aneurysm in European and Japanese populations. Nat Genet 2008; 40: 1472–1477.
McEvoy BP, Montgomery GW, McRae AF et al: Geographical structure and differential natural selection among North European populations. Genome Res 2009; 19: 804–814.
Aulchenko YS, Ripatti S, Lindqvist I et al: Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts. Nat Genet 2009; 41: 47–55.
Swertz MA, de Brock EO, van Hijum S et al: Molecular Genetics Information System (MOLGENIS): alternatives in developing local experimental genomics databases. Bioinformatics 2004; 20: 2075–2083.
Freedman ML, Reich D, Penney KL et al: Assessing the impact of population stratification on genetic association studies. Nat Genet 2004; 36: 388–393.
Tian C, Gregersen PK, Seldin MF : Accounting for ancestry: population substructure and genome-wide association studies. Hum Molec Genet 2008; 17: R143–R150.
Yu K, Wang Z, Li Q et al: Population substructure and control selection in genome-wide association studies. PLoS ONE 2008; 3: e2551.
Salmela E, Lappalainen T, Fransson I et al: Genome-wide analysis of single nucleotide polymorphisms uncovers population structure in Northern Europe. PLoS ONE 2008; 3: e3519.
Purcell S, Neale B, Todd-Brown K et al: PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 2007; 81: 559–575.
Price AL, Weale ME, Patterson N et al: Long-range LD can confound genome scans in admixed populations. Am J Hum Genet 2008; 83: 132–135.
Nevanlinna HR : The Finnish population structure. A genetic and genealogical study. Hereditas 1972; 71: 195–235.
Varilo T, Laan M, Hovatta I et al: Linkage disequilibrium in isolated populations: Finland and a young sub-population of Kuusamo. Eur J Hum Genet 2008; 8: 604–612.
Guillot G, Santos F, Estoup A : Inference in population genetics with Geneland: a sensitivity analysis to spatial sampling scheme, null alleles and isolation by distance, 2009. Submitted.
Marchini J, Howie B, Myers S, McVean G, Donnelly P : A new multipoint method for genome-wide association studies via imputation of genotypes. Nat Genet 2007; 39: 906–913.
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: 904–909.
Acknowledgements
Ilkka Lappalainen from EBI is thanked for discussions over the project. NordicDB is financially supported by the Nordic Center of Excellence in Disease Genetics, Wallenberg Foundation, FP6 coordinated action PHOEBE (Promoting Harmonization of Epidemiological Biobanks in Europe), the Wallenberg Consortium North, Sweden, Center of Excellence for Complex Disease Genetics of the Academy of Finland (grants 213506 and 129680) the Biocentrum Helsinki Foundation, The Nordic Centre of Excellence (NCoE) Programme in Molecular Medicine. KH acknowledges support from the Swedish Research Council (grant number 523-2006-972).
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Leu, M., Humphreys, K., Surakka, I. et al. NordicDB: a Nordic pool and portal for genome-wide control data. Eur J Hum Genet 18, 1322–1326 (2010). https://doi.org/10.1038/ejhg.2010.112
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DOI: https://doi.org/10.1038/ejhg.2010.112
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