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MESA Family Ancillary Study Update

MESA Family Ancillary Study Update. Jerome I. Rotter Tuesday, 9/19/06. Family Component. Overview of Progress MESA Family. Progress in phenotypic data acquisition and cleaning 1,981 cell lines now established (or being transformed) as of 9/7/2006

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MESA Family Ancillary Study Update

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  1. MESA Family Ancillary Study Update Jerome I. Rotter Tuesday, 9/19/06

  2. Family Component

  3. Overview of ProgressMESA Family • Progress in phenotypic data acquisition and cleaning • 1,981 cell lines now established (or being transformed) as of 9/7/2006 • Supplemental funding for the genome screen has been requested

  4. Sibpair Accrual – Overall Expected All Sites Actual All Sites

  5. Sibpair Accrual – By Site

  6. Phenotypic Data Acquisition As of 8/31/06 [1] As of 9/7/06. Includes a few number of probands and parents with cell lines.

  7. Genetic Plan • Recruitment of families • Wonderfully well .. Congrats to all! • Two general types of analyses • Phenotypic (including environmental covariates) • Familial Aggregation (heritability) • Bivariate (genetic/environmental correlations) • Genotypic • Candidate Gene (family-based association) • Genome-wide Linkage Scan (6K SNP panel)

  8. Familial Aggregation Analyses • Raffel presentation • MESA Family Steering Committee meeting and MESA Steering Committee meeting • Focus of Pankow presentation • MESA Family Steering Committee meeting

  9. Genome Wide Linkage Scan • Originally planned to utilize Mammalian Genotyping Service  nolonger available • Plan: Supplemental funding request • Bids for genome screen solicited from deCode, Prevention Genetics, Illumina • Recommended 6000 SNP Illumina panel to NHLBI: • Increased SNP density for information content when parents are not available* *Hum Mol Genet 2004 13:1943-9

  10. Candidate Gene Component

  11. Progress on Candidate Genes • 6 manuscripts from “prior” candidate genes analyses in or pending publication (prior to MESA Family large-scale genotyping effort) • Phase 2 genotyping  underway • Phase 1 genes  prelim analysis • Genepage  going live

  12. History Genetic Studies in MESA Family • Originally proposed to genotype 6-8 candidate genes with ~80 SNPs in MESA (parent study) and • Genome scan in MESA Family subjects • Rapid technological developments  greater scope for the same budget Now, two phases of genotyping

  13. Candidate Genes • Phase 1 ( ~720 subjects in each ethnicity/race) • 120 candidate genes • 1536 SNPs including 96 AIMs • Phase 2 (same subjects as phase 1) • Selection of another 1536 SNPs

  14. Publications Process

  15. Publications Process • Lead & senior authors for 41 proposals have been identified • More to come: • Phenotypes narrowed and made specific • Additional authors are identified in MESA groups

  16. Publications Process • In order not to burden the existing MESA P&P: • Formation of separate Genetics P&P Committee to be proposed to the Steering Committee at this meeting • Collate authors, genes, & phenotypes • Help lead author to find other investigators interested in a particular gene/phenotype combination • Make gene/phenotype data available

  17. Publications Process Lead Authors • Once approved, lead author will be asked to confirm acceptance of gene/phenotype assignment • Lead author will be given access to the genetic & phenotype data by the Coordinating Center upon acceptance • Lead develops paper proposal for MESA P&P Committee

  18. NHLBI CARE Study

  19. Summary: CARE Study • Goal: 1700 candidate genes (8-10 SNPs per gene); 15,000 markers on ~50,000 participants from eight NHLBI funded-studies • Comparatively smaller sample for genome-wide association ARIC - Atherosclerosis Risk In Communities CARDIA - Coronary Artery Risk Development in Young Adults CHS - Cardiovascular Health Study CSSCD - The Cooperative Study of Sickle Cell Disease FHS - Framingham Heart Study JHS - Jackson Heart Study MESA - Multi-Ethnic Study of Atherosclerosis SHHS - Sleep Heart Health Study

  20. Larry Atwood, Boston, MAFHS Eric Boerwinkle, Houston, TXARIC Richard Fabsitz, Bethesda, MDNHLBI Myriam Fornage, Houston, TXCARDIA Stacey Gabriel, Cambridge, MABroad Joel Hirschhorn, Cambridge, MABroad Ronald Krauss, Oakland, CAHeart Abdullah Kutlar, August, GABlood Deborah Meyers, Winston-Salem, NCLung Emanual Mignot, Palo Alto, CASleep Dina Paltoo, Bethesda, MDNHLBI Susan Redline, Cleveland, OHSHHS Jerome Rotter, Los Angeles, CAMESA Jeanne Smith, Englewood, NJCSSCD Russell Tracy, Colchester, VTCHS James Wilson, Jackson, MSJHS CARE Steering Committee

  21. Susan Heckbert Craig Johnson Richard Kronmal Kiang Liu Joe Mychaleckyj James Pankow Wendy Post Bruce Psaty Stephen Rich Jerome Rotter Kent Taylor Russell Tracy Michael Tsai MESA CARE Working Group

  22. Data Release/IRB - James Wilson (Chair) - Rotter, Liu DNA Transfer/Genotyping - Larry Atwood (Chair) - Tsai Analysis/Study Design - Stephen Rich (Chair) - Pankow Candidate Gene/SNP Selection - Myriam Fornage (Chair) - Taylor, Tsai Phenotypes - Bruce Psaty (co-Chair)- Susan Heckbert (co-Chair) - Liu Informatics - Joe Mychaleckyj (Chair) Publications- to be determined (Chair) - Post CARE Subcommittees

  23. General CARE Timeline • Set up infrastructure at Broad and Steering/ Subcommittees • Determine protocol for Pilot Study • Pilot Study • Candidate Gene Study • Whole Genome Association Study

  24. CARE Draft Data Distribution Policy and Data Access Agreement • NHLBI goal • Comprehensive genotype and phenotype data set • Broadly accessible to the scientific community • Protect interest of study participants • Promote productivity of CARE Cohort Investigators • Based on Framingham SHARE policy • Will be submitted to each Cohort’s Ancillary Studies Committee and local IRBs for approval

  25. CARE Draft Data Distribution Policy and Data Access Agreement • If approval can not be reached, options include • Re-consent if funding available • Data Enclave model (investigator-driven analysis but not raw genotyping download) • Withdrawal of the study from CARE • CARE will provide final documents and IRB talking points

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