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.

• 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.aspx

NHLBI SHARe website (not much info).

• http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gap dbGaP.

Characteristics Black (n=8515) Hispanics (n=3642)

Age at enrollment

50-54 1,513 873

55-59 2,009 960

60-69 3,681 1,434

70-79 1,312 375

Component

OS 3,869 1,754

HT 1,856 998

DM 3,484 1,220

Cad 2,390 1,078

Region

Northeast 1,489 453

South 4,171 1,479

Midwest 1,997 138

West 858 1,572