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MESA Large-Scale External Genetic Collaborations SHARe, CARe, and SEA

Explore the large-scale genetic collaborations MESA, CARe, and SHARe, which aim to analyze genetic variation in cardiovascular, lung, blood, and sleep traits. These collaborations involve genotyping and phenotype collection across multiple cohorts.

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MESA Large-Scale External Genetic Collaborations SHARe, CARe, and SEA

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  1. MESA Large-Scale External Genetic CollaborationsSHARe, CARe, and SEA MESA Steering Committee February 2008

  2. MESA and MESA Family • Can be considered a platform for large-scale genetic collaborations • 3 such collaborations are active or in development SEA, March 2006 CARe, May 2006 SHARe, in development

  3. The NHLBI’s Candidate Gene Association Resource: CARe

  4. Candidate Gene Association Resource: CARe • GOAL: Cross-cohort analysis of genetic variation in important cardiovascular, lung, blood, sleep traits • Genotyping of ~50,000 DNAs • Phenotype collection and distribution • 9 CARe cohorts

  5. CARe Genotyping Plan PILOT (Sequenom) • 35 SNPs typed on ~50,000 DNAs from all CARe Cohorts Phase II (Illumina iSelect – IBC Chip) • ~49,000 SNPs covering ~2100 genes typed on ~50,000 DNAs from all CARe Cohorts Phase III (Affymetrix Human Chip version 6.0) • ~1,000,000 SNPs (plus CNVs) typed on ~11,000 DNAs from African-American participants in ARIC, CARDIA, Cleveland Family, JHS and MESA Slide courtesy of Deb Farlow

  6. Current Status of CARe • Pilot: 50k samples, 35 SNPs • MESA DNAs shipped to Broad • Genotyping is in progress • 25 “pilot” phenotypes selected and data provided • Phase 2: 50k samples, 49k SNPs • Transfer of all phenotypes • Genotyping to begin Spring 2008 • Phase 3: 11k African American samples • Affymetrix 1mil chip GWA genotyping in progress

  7. Current Status of CARe • Working groups established, MESA well represented • Initial analyses will use the MESA-developed model of candidate wide association approaches

  8. CARe Working Groups

  9. SNP Health Association Resource (SHARe)

  10. SHARe Cohorts • Framingham SHARe • 9,000 subject from Framingham Heart Study • 550k Affymetrix GWA chip • MESA SHARe • 8,470 subjects from MESA, MESA Family, and MESA Air • 1 mil Affymetrix GWA chip

  11. SHARe • GOAL: understand the genetic contributions to the etiologies and natural history of subclinical cardiovascular disease and related disorders • Data distribution through dbGAP at the NCBI • Non-MESA Investigators have 1 year moratorium on submission for publication,but receive the data at the same time

  12. Current MESA SHARe Timeline Negotiation and Basic Terms acceptable to NHLBI and MESA IRB approval Delivery of DNA to Affymetrix Receipt of GW data from Affymetrix (Preliminary Cleaning) PhenotypesExams 1 – 3, MESA Family, Ancillary studies Additional PhenotypesExam 4, Ancillary studies, Clinical Events Thoroughly cleaned GW dataset to NCBI dbGAP Updates with ancillary studies and clinical events June 07- Mar 08: Winter 2007: March 2008: Summer: Summer: Fall 2008: Winter 2008: Annually: Analytic efforts begins at each dbGAP data release

  13. Current Status of SHARe • Approval by Steering Committee, Ancillary Studies Committee, and OSMB • 16 of 17 IRB approvals completed • Negotiation of contractual terms is ongoing

  14. Burden/Opportunity of Large-Scale External Genetic Collaborations • Additional MESA representation on CARe phenotype working groups is welcome • CARe IRB approvals are consistent with old NHLBI genetic data sharing policy, but not new NIH policy • SHARe IRB approvals have been obtained under old NIH policy; exemption request being crafted

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