Multiple independent genetic factors at NOS1AP modulate the QT interval in a multi-ethnic population.
Extremes of electrocardiographic QT interval are associated with increased risk for sudden cardiac death (SCD); thus, identification and characterization of genetic variants that modulate QT interval may elucidate the underlying etiology of SCD. Previous studies have revealed an association between...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2009-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2628730?pdf=render |
| _version_ | 1818526589524115456 |
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| author | Dan E Arking Amit Khera Chao Xing W H Linda Kao Wendy Post Eric Boerwinkle Aravinda Chakravarti |
| author_facet | Dan E Arking Amit Khera Chao Xing W H Linda Kao Wendy Post Eric Boerwinkle Aravinda Chakravarti |
| author_sort | Dan E Arking |
| collection | DOAJ |
| description | Extremes of electrocardiographic QT interval are associated with increased risk for sudden cardiac death (SCD); thus, identification and characterization of genetic variants that modulate QT interval may elucidate the underlying etiology of SCD. Previous studies have revealed an association between a common genetic variant in NOS1AP and QT interval in populations of European ancestry, but this finding has not been extended to other ethnic populations. We sought to characterize the effects of NOS1AP genetic variants on QT interval in the multi-ethnic population-based Dallas Heart Study (DHS, n = 3,072). The SNP most strongly associated with QT interval in previous samples of European ancestry, rs16847548, was the most strongly associated in White (P = 0.005) and Black (P = 3.6 x 10(-5)) participants, with the same direction of effect in Hispanics (P = 0.17), and further showed a significant SNP x sex-interaction (P = 0.03). A second SNP, rs16856785, uncorrelated with rs16847548, was also associated with QT interval in Blacks (P = 0.01), with qualitatively similar results in Whites and Hispanics. In a previously genotyped cohort of 14,107 White individuals drawn from the combined Atherosclerotic Risk in Communities (ARIC) and Cardiovascular Health Study (CHS) cohorts, we validated both the second locus at rs16856785 (P = 7.63 x 10(-8)), as well as the sex-interaction with rs16847548 (P = 8.68 x 10(-6)). These data extend the association of genetic variants in NOS1AP with QT interval to a Black population, with similar trends, though not statistically significant at P<0.05, in Hispanics. In addition, we identify a strong sex-interaction and the presence of a second independent site within NOS1AP associated with the QT interval. These results highlight the consistent and complex role of NOS1AP genetic variants in modulating QT interval. |
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| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T06:25:07Z |
| publishDate | 2009-01-01 |
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| spelling | doaj.art-b6c05b58ad19414d8b906bcbe9296bac2022-12-22T01:17:41ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-0141e433310.1371/journal.pone.0004333Multiple independent genetic factors at NOS1AP modulate the QT interval in a multi-ethnic population.Dan E ArkingAmit KheraChao XingW H Linda KaoWendy PostEric BoerwinkleAravinda ChakravartiExtremes of electrocardiographic QT interval are associated with increased risk for sudden cardiac death (SCD); thus, identification and characterization of genetic variants that modulate QT interval may elucidate the underlying etiology of SCD. Previous studies have revealed an association between a common genetic variant in NOS1AP and QT interval in populations of European ancestry, but this finding has not been extended to other ethnic populations. We sought to characterize the effects of NOS1AP genetic variants on QT interval in the multi-ethnic population-based Dallas Heart Study (DHS, n = 3,072). The SNP most strongly associated with QT interval in previous samples of European ancestry, rs16847548, was the most strongly associated in White (P = 0.005) and Black (P = 3.6 x 10(-5)) participants, with the same direction of effect in Hispanics (P = 0.17), and further showed a significant SNP x sex-interaction (P = 0.03). A second SNP, rs16856785, uncorrelated with rs16847548, was also associated with QT interval in Blacks (P = 0.01), with qualitatively similar results in Whites and Hispanics. In a previously genotyped cohort of 14,107 White individuals drawn from the combined Atherosclerotic Risk in Communities (ARIC) and Cardiovascular Health Study (CHS) cohorts, we validated both the second locus at rs16856785 (P = 7.63 x 10(-8)), as well as the sex-interaction with rs16847548 (P = 8.68 x 10(-6)). These data extend the association of genetic variants in NOS1AP with QT interval to a Black population, with similar trends, though not statistically significant at P<0.05, in Hispanics. In addition, we identify a strong sex-interaction and the presence of a second independent site within NOS1AP associated with the QT interval. These results highlight the consistent and complex role of NOS1AP genetic variants in modulating QT interval.http://europepmc.org/articles/PMC2628730?pdf=render |
| spellingShingle | Dan E Arking Amit Khera Chao Xing W H Linda Kao Wendy Post Eric Boerwinkle Aravinda Chakravarti Multiple independent genetic factors at NOS1AP modulate the QT interval in a multi-ethnic population. PLoS ONE |
| title | Multiple independent genetic factors at NOS1AP modulate the QT interval in a multi-ethnic population. |
| title_full | Multiple independent genetic factors at NOS1AP modulate the QT interval in a multi-ethnic population. |
| title_fullStr | Multiple independent genetic factors at NOS1AP modulate the QT interval in a multi-ethnic population. |
| title_full_unstemmed | Multiple independent genetic factors at NOS1AP modulate the QT interval in a multi-ethnic population. |
| title_short | Multiple independent genetic factors at NOS1AP modulate the QT interval in a multi-ethnic population. |
| title_sort | multiple independent genetic factors at nos1ap modulate the qt interval in a multi ethnic population |
| url | http://europepmc.org/articles/PMC2628730?pdf=render |
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