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Affymetrix has partnered with individual researchers and consortia to create a new, publicly available control cohort database for Affymetrix genome-wide array data. The database includes genotypes for more than 10,000 samples from a variety of ethnic backgrounds, with 5,000 to 10,000 additional samples expected to be added over the next year. The controls database will enable researchers to select age- and sex-matched controls from similar ethnic backgrounds as their cases.
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Table 1: Control Data Projects Underway Using Affymetrix Arrays |
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Investigator |
Affiliation |
Population |
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Charles Sanders |
Genetic Association Information Network (GAIN) |
Variety of samples from different ethnic origins |
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| Peter Donnelly, et al. |
Wellcome Trust Case Control Consortium (WTCCC) |
Samples from England, Scotland and Wales as part of a project spanning multiple disease areas. 1,500 samples from 1958 British Birth Cohort; 1,500 samples from UK National Blood Service. Learn more |
3,000 |
Affymetrix 500K Control Cohort Participants: |
Michael Krawczak, Stefan Schreiber |
University of Kiel - NGFN |
POPGEN Northern German population study. |
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Erich Wichmann |
GSF NGFN |
KORA-gen Southern German population study. Control subset of large population study; used as controls in more than 30 studies. |
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Peter Arner |
Karolinska Institute |
Swedish females |
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| André Uitterlinden |
Erasmus |
Dutch women living in Rotterdam |
500 |
A Resource for Case Control Studies
A large body of data from normal control samples enables researchers to potentially increase the power and reduce costs of case control association studies. Researchers will be able to select age- and sex-matched controls from a similar ethnic background as their cases, and add them to their current study to increase genetic power. The figure below shows an example power calculation for a hypothetical study, highlighting the impact of additional controls to increase genetic power.
In addition, some researchers may only genotype cases, using controls from the database to save money and effort. The validity of such an approach was recently demonstrated by the Wellcome Trust Case Control Consortium, which successfully used a set of 3,000 common controls from the UK as a control database for eight genome-wide disease scans.
Defining Genetic Diversity in European Populations
European researchers, led by Manfred Kaiser of Erasmus MC and Michael Krawczak of the University of Kiel, have agreed to work together to analyze their data and identify markers that could be used to identify different genetic subpopulations in Europe—a first step towards understanding population stratification and admixture on a global scale.
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Figure 1: Multidimensional scaling analysis of pair-wise Y-STR based FST between 91 male European samples. Displayed are the first three dimensions, which together account for 96.4 percent of the variance. Sample locations are marked in black; color coding is on an arbitrary “rainbow” scale that allocates yellow and magenta to the opposite extremes, via green and blue (Rower, et al., 2005). |
Control Data Set Sample Eligibility
Two types of samples will be eligible for inclusion in the controls database: a random selection of a population without respect to phenotype, and unaffected individuals in a case control study. For example, if 500 cases and 500 controls were genotyped in an association study for Parkinson's disease, the 500 disease samples would not be eligible for the controls database. The minimal sample contribution is 200, and must meet the criteria below:
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Samples must be from a random sampling of the population, selected without respect to phenotype, or must be unaffected individuals from a case control study. |
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Proper consent and Institutional Review Board (IRB) approval must be in place for release of the genotype information to any scientific researcher with a legitimate scientific or commercial research purpose. |
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Researcher must provide the gender, ethnic background and age for each sample. |
Access to the Data
The National Center for Biotechnology Information (NCBI) at the National Institutes of Health has recently agreed to house the control cohort database like from the GAIN initiative or the Affymetrix control cohort program, with a procedure to ensure proper informed consent for access to the data. Under this system, a user would select a data set and be directed to the owner of the sample collection. Information would then be submitted to show that the data would be used for a scientific project that meets the terms of the patient consent. Upon approval, the NCBI would grant the requestor access to the data.
Adding Data to the Controls Database
Affymetrix and other members of the consortium are actively working to expand the samples in the database, and to support similar cross-study genotype databases in Europe and Asia.
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