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SHARe. What is WHI-SHARe?. SHARe – stands for SNP Health Association Resource. It is an NHLBI program for genome-wide association studies (GWAS). GWAS studies carried out as part of SHARe will be a resource for the scientific community.
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What is WHI-SHARe? • SHARe – stands for SNP Health Association Resource. • It is an NHLBI program for genome-wide association studies (GWAS). GWAS studies carried out as part of SHARe will be a resource for the scientific community. • WHI is part of this program, as approximately 12,000 WHI minority subjects are “GWASed” as part of SHARe.
What is a GWAS? • Our genome is several billion basepairs (A/C/G/T) long. • All of us are the same in the large majority of these basepairs. • The most common variation are Single Nucleotide Polymorphisms (SNPs), locations in the genome where people differ in a single basepair. • GWAS employs technologies that can measure these variations in up to 1,000,000 locations.
What is a GWAS? • Using a GWAS of cases and controls of a particular outcome, we can do association tests to see whether this location in the genome is associated with the outcome • Because of dependence (linkage disequilibrium) in the genome these 1000000 SNPs cover almost the complete genome • There are many other issues: methodological, QC, data analysis, multiple testing, population stratification, epistasis, gene x environment interactions, …. Not today.
What is WHI SHARe? • A GWAS on the Affy 6.0 platform (~1,000,000 SNPs) on a cohort of 8,515 African American and 3,642 Hispanics. • These are the AA and Hispanic participants that either signed the supplemental consent, or were deceased at the time of the supplemental consent. • These participants were not selected for a particular outcome. • Note: there are other GWAS studies ongoing or planned in WHI.
SHARe data • WHI-SHARe data will not be available on any of the WHI websites. • Currently the SHARe data is being cleaned simultaneously by the CCC and NCBI (NIH). • The CCC is organizing the public access dataset to be linked to the SHARe data. • This linking will happen by NCBI. • After the linking is complete the data will be available on dbGaP, an NIH database.
Getting the data • The data is expected to be on dbGaP in the fall. • Everyone can get the data from dbGaP. • It requires an IRB approval of your local institution, and then approval by an NIH Data Access Committee (DAC). • Everyone can analyze the data, but WHI investigators have one year protected time for publishing papers (more later). • Analysis of WHI-SHARe dbGaP data cannot involve other WHI (e.g. ancillary study) data.
But how about my … data? • Only the public access data will be linked to the SHARe GWAS data now. • Other data (e.g. ancillary studies, BAAs) can – and will – be linked at a later stage. • Which study will be linked when depends on resources, need (papers using this data have been proposed), and available information (e.g. sampling framework). • We expect that the WHI SHARe dbGaP data will be updated on a regular basis. • Whenever new data elements are added, WHI investigators again have 1 year “protected time”.
Writing WHI SHARe papers • Papers fall under WHI P&P regulations. • Paper proposals should take particular care of • Possibility of replication / confirmation in other studies. • Power: is there a reasonable chance of finding an effect after correcting for 1,000,000 tests. • Which variables are used: currently only data in the public access data will be available as part of the dbGaP dataset. • Some discussion showing the authors are aware of issues related to the scale of the computations, population stratification, etc.
Analysis of WHI-SHARe papers • As the analysis of WHI-SHARe papers does not involve data from the WHI database, any site can have the data to do it. • As the analysis of GWAS data is sometimes non standard, and certainly large, not every site may have the equipment and personnel resources to do it. • WHI/NHLBI is establishing four “analytic centers” that will carry out analyses for WHI-SHARe papers during the first “protected year”. • These four analytic centers will communicate regularly to share information, data, code …
Analysis of WHI-SHARe papers • The WHI P&P will “assign” which WHI-SHARe paper is analyzed by which analytic center. • Other groups are free to analyze the WHI-SHARe data themselves for an approved WHI paper, provided the WHI P&P believes the group has the ability to do such an analysis. • For groups doing there own analysis there is no additional (financial) support, beyond the small amount of support always provided to lead authors of WHI papers.
Timeline of WHI-SHARe • November 08 – ~May 09: processing of DNA, genotyping. • March 09 – ~August 09: cleaning of genotype data, preparing of exposure data. • ~June 09: analytic centers start up. • Fall 09: posting of WHI-SHARe data on dbGaP. • Fall 09-Fall 10: protected time for WHI investigators to write papers using WHI-SHARe data
Information • WHIOPS: whiops data datasets common IDs of SHARe participants – allows you to link with other data sets when preparing paper proposals. • http://public.nhlbi.nih.gov/GeneticsGenomics/home/share.aspxNHLBI SHARe website (not much info). • http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gap dbGaP.