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Genome-wide joint SNP and CNV analysis of aortic root diameter in African Americans: the HyperGEN study
Nathan E Wineinger1, Amit Patki, Kristin J Meyers
1Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA. nwineing@uab.edu
Insights
Researchers identified novel genetic regions associated with aortic root diameter in African Americans. This study highlights potential genetic factors contributing to cardiovascular disease risk in this understudied population.
Area of Science:
- Genetics
- Cardiovascular Disease Research
- Population Genomics
Background:
- Aortic root diameter is crucial for understanding aortic regurgitation and dissection risk.
- African Americans face a high burden of cardiovascular diseases and are underrepresented in genetic studies.
- The HyperGEN study provided a cohort for investigating genetic determinants of aortic root diameter.
Purpose of the Study:
- To conduct a genome-wide association study (GWAS) for aortic root diameter in African Americans.
- To identify novel genetic variants influencing aortic root diameter.
- To explore the combined effects of single nucleotide polymorphism (SNP) alleles and copy number variations (CNVs).
Main Methods:
- Employed a two-stage, mixed-model procedure for genome-wide analysis.
- Jointly tested for SNP allele and CNV effects.
- Utilized data from African American participants in the HyperGEN study.
Main Results:
- Identified significant genetic associations on chromosome 7 between CRCP and KCTD7 genes (p = 4.26 × 10(-7)).
- Discovered novel genetic contributors on chromosome 20 between SIRPA and PDYN genes (p = 3.28 × 10(-8)).
- These regions represent potential novel genetic factors influencing aortic root diameter.
Conclusions:
- The identified genomic regions are promising candidates for further research into cardiovascular outcomes in African Americans.
- The applied methodology offers a framework for genetic studies investigating joint SNP and CNV effects.
- This research contributes to understanding the genetic architecture of aortic root diameter in a high-risk population.
Background:
Aortic root diameter is a clinically relevant trait due to its known relationship with the pathogenesis of aortic regurgitation and risk for aortic dissection. African Americans are an understudied population despite a particularly high burden of cardiovascular diseases. We report a genome-wide association study on aortic root diameter among African Americans enrolled in the HyperGEN study. We invoked a two-stage, mixed model procedure to jointly identify SNP allele and copy number variation effects.
Results:
Results suggest novel genetic contributors along a large region between the CRCP and KCTD7 genes on chromosome 7 (p = 4.26 × 10(-7)); and the SIRPA and PDYN genes on chromosome 20 (p = 3.28 × 10(-8)).
Conclusions:
The regions we discovered are candidates for future studies on cardiovascular outcomes, particularly in African Americans. The methods we employed can also provide an outline for genetic researchers interested in jointly testing SNP and CNV effects and/or applying mixed model procedures on a genome-wide scale.
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