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, 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

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)29-40
Number of pages12
JournalAnnals of Noninvasive Electrocardiology
Volume18
Issue number1
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

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Hispanic Americans
Ethnic Groups
Single Nucleotide Polymorphism
Atherosclerosis
Sudden Cardiac Death
Genome-Wide Association Study
African Americans
Population
Linear Models
Electrocardiography
Cardiovascular Diseases
Heart Rate
Alleles

Keywords

  • arrhythmia
  • electrocardiography
  • electrophysiology
  • genetics

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Associations between NOS1AP single nucleotide polymorphisms (SNPs) and QT interval duration in four racial/ethnic groups in the Multi-Ethnic Study of Atherosclerosis (MESA). / Shah, Sidharth A.; Herrington, David M.; Howard, Timothy D.; Divers, Jasmin; Arnett, Donna K.; Burke, Greg L.; Hong Kao, Weng; Guo, Xiuqing; Siscovick, David S.; Chakravarti, Aravinda; Lima, Joao A.; Psaty, Bruce M.; Tomaselli, Gordon F.; Rich, Stephen S.; Bowden, Donald W.; Post, Wendy.

In: Annals of Noninvasive Electrocardiology, Vol. 18, No. 1, 01.01.2013, p. 29-40.

Research output: Contribution to journalArticle

Shah, SA, Herrington, DM, Howard, TD, Divers, J, Arnett, DK, Burke, GL, Hong Kao, W, Guo, X, Siscovick, DS, Chakravarti, A, Lima, JA, Psaty, BM, Tomaselli, GF, Rich, SS, Bowden, DW & Post, W 2013, 'Associations between NOS1AP single nucleotide polymorphisms (SNPs) and QT interval duration in four racial/ethnic groups in the Multi-Ethnic Study of Atherosclerosis (MESA)', Annals of Noninvasive Electrocardiology, vol. 18, no. 1, pp. 29-40. https://doi.org/10.1111/anec.12028
Shah, Sidharth A. ; Herrington, David M. ; Howard, Timothy D. ; Divers, Jasmin ; Arnett, Donna K. ; Burke, Greg L. ; Hong Kao, Weng ; Guo, Xiuqing ; Siscovick, David S. ; Chakravarti, Aravinda ; Lima, Joao A. ; Psaty, Bruce M. ; Tomaselli, Gordon F. ; Rich, Stephen S. ; Bowden, Donald W. ; Post, Wendy. / Associations between NOS1AP single nucleotide polymorphisms (SNPs) and QT interval duration in four racial/ethnic groups in the Multi-Ethnic Study of Atherosclerosis (MESA). In: Annals of Noninvasive Electrocardiology. 2013 ; Vol. 18, No. 1. pp. 29-40.
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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.",
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T1 - Associations between NOS1AP single nucleotide polymorphisms (SNPs) and QT interval duration in four racial/ethnic groups in the Multi-Ethnic Study of Atherosclerosis (MESA)

AU - Shah, Sidharth A.

AU - Herrington, David M.

AU - Howard, Timothy D.

AU - Divers, Jasmin

AU - Arnett, Donna K.

AU - Burke, Greg L.

AU - Hong Kao, Weng

AU - Guo, Xiuqing

AU - Siscovick, David S.

AU - Chakravarti, Aravinda

AU - Lima, Joao A.

AU - Psaty, Bruce M.

AU - Tomaselli, Gordon F.

AU - Rich, Stephen S.

AU - Bowden, Donald W.

AU - Post, Wendy

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N2 - 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.

AB - 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.

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