Common nos1ap genetic variation and qt interval duration in african americans
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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

Common NOS1AP genetic variation and QT interval duration in African Americans

Sara Tribune

Tougaloo College

Summer Research Program in Genomics


Sudden cardiac death
Sudden cardiac death

300,000 deaths/yr US

Risk factors inadequate

2


Prolonged qt intervals
Prolonged QT intervals

  • Increased risk of Sudden Cardiac Death

  • Long QT Syndrome and Short QT Syndrome

  • Drug-induced arrhythmias


Electrocardiograms
Electrocardiograms

http://www.mercksource.com/pp/us/cns/cns_hl_adam

.jspzQzpgzEzzSzppdocszSzuszSzcnszSzcontentzSzadamzSzimagepageszSz8772zPzhtm


Qt interval is heritable
QT-Interval is Heritable

Framingham Heart Study (FHS)

European descent (ED)

35% heritable

Jackson Heart Study (JHS)

African descent (AD)

40-41% heritable

.


Nos1ap associated with qt interval duration in ed
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.


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?


The structure of haplotype blocks in the human genome. between QT interval duration and

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


Replication of the nos1ap association in african americans
Replication of the NOS1AP association in African Americans. between QT interval duration and

1st Step

  • Selection of SNPs

    2nd Step

  • Genotyping of SNPs

  • Determine locus-specific ancestry

  • Interim analysis

    Final Step

  • Final data analysis


African variants show less correlation
African Variants Show Less Correlation between QT interval duration and

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


Study design
Study Design between QT interval duration and

CEU Data

37 SNPs were correlated to rs10494366 in CEU (European data)


rs10494366 between QT interval duration and

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).


Locus specific ancestry increases statistical power
Locus-Specific Ancestry Increases Statistical Power between QT interval duration and

Locus-specific ancestry

African Descent

European Descent

{ } NOS1AP Locus { } NOS1AP Locus { }

Afr-Afr

67.24 %

Afr-Eur

29.52 %

Eur-Eur

3.24 %


Genotyping
Genotyping between QT interval duration and


Initial genotyping in 4605 jhs individuals
Initial genotyping in 4605 JHS Individuals between QT interval duration and


Possible outcomes
Possible Outcomes between QT interval duration and


Progress
Progress between QT interval duration and

Study Design

Selection of SNPs

Selection and formation of assay pools

Genotyped SNPs

Interim analysis (In Progress)

Final data analysis (August 15)


Acknowledgments between QT interval duration and

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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