Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Jan;18(1):29-40.
doi: 10.1111/anec.12028.

Associations between NOS1AP single nucleotide polymorphisms (SNPs) and QT interval duration in four racial/ethnic groups in the Multi-Ethnic Study of Atherosclerosis (MESA)

Sidharth A Shah  1 , David M Herrington, Timothy D Howard, Jasmin Divers, Donna K Arnett, Greg L Burke, Weng Hong Kao, Xiuqing Guo, David S Siscovick, Aravinda Chakravarti, Joao A Lima, Bruce M Psaty, Gordon F Tomaselli, Stephen S Rich, Donald W Bowden, Wendy Post
Affiliations

Associations between NOS1AP single nucleotide polymorphisms (SNPs) and QT interval duration in four racial/ethnic groups in the Multi-Ethnic Study of Atherosclerosis (MESA)

Sidharth A Shah et al. Ann Noninvasive Electrocardiol. 2013 Jan.

Abstract

Backgrounds: QT is a risk factor for sudden cardiac death (SCD). A genome-wide association study identified NOS1AP variants associated with QT, which have been replicated in predominantly Caucasian (CAU) populations. We used the Multi-Ethnic Study of Atherosclerosis to examine association of QT with NOS1AP variants in an ethnically diverse cohort.

Methods: Twenty-eight tagging SNPs spanning NOS1AP were genotyped in 2847 MESA participants (approximately equal numbers of CAU, African Americans (AFA), Hispanics (HIS), and Chinese (CHN)), age 45-84 years, without cardiovascular disease. QT was measured using 12-lead ECG. Associations between QT and NOS1AP variants were evaluated using linear regression, adjusted for heart rate, age, gender, and field center stratified by ancestry, using an additive inheritance model. Ancestry informative markers (AIMs) and principal components using AIMs were used as additional covariates.

Results: More NOS1AP SNPs were associated with QT in CAU than the other races. In CAU, each copy of rs1932933 risk allele was associated with an increase in QT (4.9 msec, P = 7.20 × 10-7). Significant associations in CAU and HIS were located at the 5' end, while associations in CHN were located at the 3' end.

Conclusions: NOS1AP variants were associated with QT in CAU, with weaker evidence for selected variants in HIS and CHN. Location of significant SNPs varied across ancestry. We identified possible novel associations at the 3' end of NOS1AP, where we observed significant association with QT in CHN only. Genotyping within these regions may determine functional variants affecting QT and SCD risk. In addition, investigations are needed across ethnically diverse population cohorts.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Race‐specific associations (‐Log10(P value)) for each SNP across NOS1AP. Red markers (adjusted model) represent the P values for each SNP‐trait association with respect to the nominal and Bonferroni‐adjusted alpha levels (0.05 and 0.002, respectively). LD structure (r 2) is shown below.
Figure 2
Figure 2
QT residuals vs. number of risk alleles summed across all nominally significant SNPs. The y‐axis is the residual QT after adjusting for HR, age, gender, MESA field site, QT altering medications, and population stratification.
See this image and copyright information in PMC

References

    1. Thom T, Haase N, Rosamond W, et al. Heart disease and stroke statistics–2006 update: A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2006;113:e85–151. - PubMed
    1. Arking DE, Junttila MJ, Goyette P, et al. Identification of a sudden cardiac death susceptibility locus at 2q24.2 through genome‐wide association in European ancestry individuals. PLoS Genet 2011;7:e1002158. - PMC - PubMed
    1. Schouten EG, Dekker JM, Meppelink P, et al. Qt inter‐val prolongation predicts cardiovascular mortality in an apparently healthy population. Circulation 1991;84:1516–1523. - PubMed
    1. Dekker JM, Crow RS, Hannan PJ, et al. Heart rate‐corrected Qt interval prolongation predicts risk of coronary heart disease in black and white middle‐aged men and women: The aric study. J Am Coll Cardiol 2004;43:565–571. - PubMed
    1. Okin PM, Devereux RB, Howard BV, et al. Assessment of Qt interval and Qt dispersion for prediction of all‐cause and cardiovascular mortality in american indians: The strong heart study. Circulation 2000;101:61–66. - PubMed

Publication types

MeSH terms

Substances