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Common NOS1AP genetic variation and QT interval duration in African Americans

Common NOS1AP genetic variation and QT interval duration in African Americans. Sara Tribune Tougaloo College Summer Research Program in Genomics. Sudden cardiac death. 300,000 deaths/yr US Risk factors inadequate. 2. Prolonged QT intervals. Increased risk of Sudden Cardiac Death

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Common NOS1AP genetic variation and QT interval duration in African Americans

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  1. Common NOS1AP genetic variation and QT interval duration in African Americans Sara Tribune Tougaloo College Summer Research Program in Genomics

  2. Sudden cardiac death 300,000 deaths/yr US Risk factors inadequate 2

  3. Prolonged QT intervals • Increased risk of Sudden Cardiac Death • Long QT Syndrome and Short QT Syndrome • Drug-induced arrhythmias

  4. Electrocardiograms http://www.mercksource.com/pp/us/cns/cns_hl_adam .jspzQzpgzEzzSzppdocszSzuszSzcnszSzcontentzSzadamzSzimagepageszSz8772zPzhtm

  5. QT-Interval is Heritable Framingham Heart Study (FHS) European descent (ED) 35% heritable Jackson Heart Study (JHS) African descent (AD) 40-41% heritable .

  6. NOS1AP Associated with QT Interval Duration in ED Three cohorts of ED individuals Common variants (rs 10494366) NOS1AP explain approximately 1.5% of QT interval variation. Whether the association between QT interval duration and common variation in NOS1AP exists in AD individuals is unknown.

  7. Why is it not accurate assume that an association exists between QT interval duration and NOS1AP in AD individuals if an association is found in in ED individuals?

  8. The structure of haplotype blocks in the human genome. Distribution of NOS1AP haplotypes Gabriel, S. B. et al. The Structure of Haplotype Blocks in the Human Genome. Science 296, 2225-2229 (2002). Courtesyof Pardis Sabeti

  9. Replication of the NOS1AP association in African Americans. 1st Step • Selection of SNPs 2nd Step • Genotyping of SNPs • Determine locus-specific ancestry • Interim analysis Final Step • Final data analysis

  10. African Variants Show Less Correlation Using Hapmap data and Haploview Correlation of SNPS in CEU (ED) and YRI (AD) data set Red=Strong Correlation White=No Correlation CEU Data YRI Data

  11. Study Design CEU Data 37 SNPs were correlated to rs10494366 in CEU (European data)

  12. rs10494366 rs4657140 rs6696160 rs1415262 rs885148 rs7548169 rs16847548 rs7550692 rs2225845 rs6696160 rs1415262 rs885148 YRI Data Study Design Tagger software selected 14 SNPs with r2 ≥0.8 in YRI (West African data).

  13. Locus-Specific Ancestry Increases Statistical Power Locus-specific ancestry African Descent European Descent { } NOS1AP Locus { } NOS1AP Locus { } Afr-Afr 67.24 % Afr-Eur 29.52 % Eur-Eur 3.24 %

  14. Genotyping

  15. Initial genotyping in 4605 JHS Individuals

  16. Possible Outcomes

  17. Progress Study Design Selection of SNPs Selection and formation of assay pools Genotyped SNPs Interim analysis (In Progress) Final data analysis (August 15)

  18. Acknowledgments Christopher Newton-Cheh Shawna Young Neal Learner Bruce Birren David Reich Funding support Broad Summer Research Program in Genomics Doris Duke Charitable Foundation (Newton-Cheh)

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