Document Details
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Document Type |
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Article In Journal |
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Document Title |
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The genetic component of bicuspid aortic valve and aortic dilation. An exome-wide association study The genetic component of bicuspid aortic valve and aortic dilation. An exome-wide association study |
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Document Language |
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English |
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Abstract |
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Background: Bicuspid aortic valve is themost common cardiovascular congenitalmalformation affecting 2% of the
general population. The incidence of life-threatening complications, the high heritability, and familial clustering
rates support the interest in identifying risk or protective genetic factors. The main objective of the present study
was to identify population-based genetic variation associatedwith bicuspid aortic valve and concomitant ascending
aortic dilation.
Materials and methods: A cross-sectional exome-wide association study was conducted in 565 Spanish cases and
484 controls. Single-marker and gene-based association analyses enriched for low frequency and rare genetic
variants were performed on this discovery stage cohort and for the subsets of cases with and without ascending
aortic dilation. Discovery-stage association signals and additional markers indirectly associated with bicuspid
aortic valve, were genotyped in a replication cohort that comprised 895 Caucasian cases and 1483 controls.
Results: Although none of the association signalswere consistent across series, the involvement of HMCN2 in calciummetabolismand
valve degeneration caused by calciumdeposit, and a nominal but not genome-wide significant
association, supported it as an interesting gene for follow-up studies on the genetic susceptibility to
bicuspid aortic valve.
Conclusions: The absence of a genome-wide significant association signal shows this valvular malformation may
be more genetically complex than previously believed. Exhaustive phenotypic characterization, even larger
datasets, and collaborative efforts are needed to detect the combination of rare variants conferring risk which,
along with specific environmental factors, could be causing the development of this disease. |
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ISSN |
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0022-2828 |
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Journal Name |
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Journal of Molecular and Cellular Cardiology |
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Volume |
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102 |
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Issue Number |
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1 |
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Publishing Year |
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1438 AH
2017 AD |
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Article Type |
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Article |
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Added Date |
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Wednesday, May 17, 2017 |
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Researchers
| Teresa Sevilla | Sevilla, Teresa | Investigator | Doctorate | |
| Christopher Newton-Cheh | Newton-Cheh, Christopher | Researcher | Doctorate | |
| Ángel Carracedo | Carracedo, Ángel | Researcher | Doctorate | |
| Daniel Muehlschlegel | Muehlschlegel, Daniel | Researcher | Doctorate | |
| David García-Dorado | García-Dorado, David | Researcher | Doctorate | |
| Simon C Body | Body, Simon C | Researcher | Doctorate | |
| Artur Evangelista | Evangelista, Artur | Researcher | Doctorate | |
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