Genetic Control of Left Atrial Gene Expression Yields Insights into the Genetic Susceptibility for Atrial Fibrillation [Original Articles]

Publication Date:
2018-03-16
Publisher:
American Heart Association (AHA)
Print ISSN:
1942-325X
Electronic ISSN:
1942-3268
Topics:
Medicine
Keywords:
Arrhythmias, Gene Expression & Regulation, Functional Genomics
Published by:
http://www.americanheart.org/
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autor Hsu, J., Gore-Panter, S., Tchou, G., Castel, L., Lovano, B., Moravec, C. S., Pettersson, G. B., Roselli, E. E., Gillinov, A. M., McCurry, K. R., Smedira, N. G., Barnard, J., Van Wagoner, D. R., Chung, M. K., Smith, J. D.
beschreibung Background: Genome-wide association studies have identified 23 loci for atrial fibrillation (AF), but the mechanisms responsible for these associations, as well as the causal genes and genetic variants, remain undefined. Methods: To identify the effect of common genetic variants on gene expression that might explain the mechanisms linking genome-wide association loci with AF risk, we performed RNA sequencing of left atrial appendages from a biracial cohort of 265 subjects. Results: Combining gene expression data with genome-wide single nucleotide polymorphism data, we found that approximately two-thirds of the expressed genes were regulated in cis by common genetic variants at a false discovery rate of 〈0.05, defined as cis-expression quantitative trait loci. Twelve of 23 reported AF genome-wide association loci displayed genome-wide significant cis -expression quantitative trait loci, at PRRX1 (chromosome 1q24), SNRNP27 (1q24), CEP68 (2p14), FKBP7 (2q31), KCNN2 (5q22), FAM13B (5q31), CAV1 (7q31), ASAH1 (8p22), MYOZ1 (10q22), C11ORF45 (11q24), TBX5 (12q24), and SYNE2 (14q23), suggesting that altered expression of these genes plays a role in AF susceptibility. Allelic expression imbalance was used as an independent method to characterize the cis-control of gene expression. One thousand two hundred forty-eight of 5153 queried genes had cis -single nucleotide polymorphisms that significantly regulated allelic expression at a false discovery rate of 〈0.05. Conclusions: We provide a genome-wide catalog of the genetic control of gene expression in human left atrial appendage. These data can be used to confirm the relevance of genome-wide association loci and to direct future functional studies to identify the genes and genetic variants responsible for complex diseases such as AF.
citation_standardnr 6208012
datenlieferant ipn_articles
feed_id 110195
feed_publisher American Heart Association (AHA)
feed_publisher_url http://www.americanheart.org/
insertion_date 2018-03-16
journaleissn 1942-3268
journalissn 1942-325X
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher American Heart Association (AHA)
quelle Circulation: Cardiovascular Genetics
relation http://circgenetics.ahajournals.org/cgi/content/short/11/3/e002107?rss=1
schlagwort Arrhythmias, Gene Expression & Regulation, Functional Genomics
search_space articles
shingle_author_1 Hsu, J., Gore-Panter, S., Tchou, G., Castel, L., Lovano, B., Moravec, C. S., Pettersson, G. B., Roselli, E. E., Gillinov, A. M., McCurry, K. R., Smedira, N. G., Barnard, J., Van Wagoner, D. R., Chung, M. K., Smith, J. D.
shingle_author_2 Hsu, J., Gore-Panter, S., Tchou, G., Castel, L., Lovano, B., Moravec, C. S., Pettersson, G. B., Roselli, E. E., Gillinov, A. M., McCurry, K. R., Smedira, N. G., Barnard, J., Van Wagoner, D. R., Chung, M. K., Smith, J. D.
shingle_author_3 Hsu, J., Gore-Panter, S., Tchou, G., Castel, L., Lovano, B., Moravec, C. S., Pettersson, G. B., Roselli, E. E., Gillinov, A. M., McCurry, K. R., Smedira, N. G., Barnard, J., Van Wagoner, D. R., Chung, M. K., Smith, J. D.
shingle_author_4 Hsu, J., Gore-Panter, S., Tchou, G., Castel, L., Lovano, B., Moravec, C. S., Pettersson, G. B., Roselli, E. E., Gillinov, A. M., McCurry, K. R., Smedira, N. G., Barnard, J., Van Wagoner, D. R., Chung, M. K., Smith, J. D.
shingle_catch_all_1 Genetic Control of Left Atrial Gene Expression Yields Insights into the Genetic Susceptibility for Atrial Fibrillation [Original Articles]
Arrhythmias, Gene Expression & Regulation, Functional Genomics
Background: Genome-wide association studies have identified 23 loci for atrial fibrillation (AF), but the mechanisms responsible for these associations, as well as the causal genes and genetic variants, remain undefined. Methods: To identify the effect of common genetic variants on gene expression that might explain the mechanisms linking genome-wide association loci with AF risk, we performed RNA sequencing of left atrial appendages from a biracial cohort of 265 subjects. Results: Combining gene expression data with genome-wide single nucleotide polymorphism data, we found that approximately two-thirds of the expressed genes were regulated in cis by common genetic variants at a false discovery rate of <0.05, defined as cis-expression quantitative trait loci. Twelve of 23 reported AF genome-wide association loci displayed genome-wide significant cis -expression quantitative trait loci, at PRRX1 (chromosome 1q24), SNRNP27 (1q24), CEP68 (2p14), FKBP7 (2q31), KCNN2 (5q22), FAM13B (5q31), CAV1 (7q31), ASAH1 (8p22), MYOZ1 (10q22), C11ORF45 (11q24), TBX5 (12q24), and SYNE2 (14q23), suggesting that altered expression of these genes plays a role in AF susceptibility. Allelic expression imbalance was used as an independent method to characterize the cis-control of gene expression. One thousand two hundred forty-eight of 5153 queried genes had cis -single nucleotide polymorphisms that significantly regulated allelic expression at a false discovery rate of <0.05. Conclusions: We provide a genome-wide catalog of the genetic control of gene expression in human left atrial appendage. These data can be used to confirm the relevance of genome-wide association loci and to direct future functional studies to identify the genes and genetic variants responsible for complex diseases such as AF.
Hsu, J., Gore-Panter, S., Tchou, G., Castel, L., Lovano, B., Moravec, C. S., Pettersson, G. B., Roselli, E. E., Gillinov, A. M., McCurry, K. R., Smedira, N. G., Barnard, J., Van Wagoner, D. R., Chung, M. K., Smith, J. D.
American Heart Association (AHA)
1942-325X
1942325X
1942-3268
19423268
shingle_catch_all_2 Genetic Control of Left Atrial Gene Expression Yields Insights into the Genetic Susceptibility for Atrial Fibrillation [Original Articles]
Arrhythmias, Gene Expression & Regulation, Functional Genomics
Background: Genome-wide association studies have identified 23 loci for atrial fibrillation (AF), but the mechanisms responsible for these associations, as well as the causal genes and genetic variants, remain undefined. Methods: To identify the effect of common genetic variants on gene expression that might explain the mechanisms linking genome-wide association loci with AF risk, we performed RNA sequencing of left atrial appendages from a biracial cohort of 265 subjects. Results: Combining gene expression data with genome-wide single nucleotide polymorphism data, we found that approximately two-thirds of the expressed genes were regulated in cis by common genetic variants at a false discovery rate of <0.05, defined as cis-expression quantitative trait loci. Twelve of 23 reported AF genome-wide association loci displayed genome-wide significant cis -expression quantitative trait loci, at PRRX1 (chromosome 1q24), SNRNP27 (1q24), CEP68 (2p14), FKBP7 (2q31), KCNN2 (5q22), FAM13B (5q31), CAV1 (7q31), ASAH1 (8p22), MYOZ1 (10q22), C11ORF45 (11q24), TBX5 (12q24), and SYNE2 (14q23), suggesting that altered expression of these genes plays a role in AF susceptibility. Allelic expression imbalance was used as an independent method to characterize the cis-control of gene expression. One thousand two hundred forty-eight of 5153 queried genes had cis -single nucleotide polymorphisms that significantly regulated allelic expression at a false discovery rate of <0.05. Conclusions: We provide a genome-wide catalog of the genetic control of gene expression in human left atrial appendage. These data can be used to confirm the relevance of genome-wide association loci and to direct future functional studies to identify the genes and genetic variants responsible for complex diseases such as AF.
Hsu, J., Gore-Panter, S., Tchou, G., Castel, L., Lovano, B., Moravec, C. S., Pettersson, G. B., Roselli, E. E., Gillinov, A. M., McCurry, K. R., Smedira, N. G., Barnard, J., Van Wagoner, D. R., Chung, M. K., Smith, J. D.
American Heart Association (AHA)
1942-325X
1942325X
1942-3268
19423268
shingle_catch_all_3 Genetic Control of Left Atrial Gene Expression Yields Insights into the Genetic Susceptibility for Atrial Fibrillation [Original Articles]
Arrhythmias, Gene Expression & Regulation, Functional Genomics
Background: Genome-wide association studies have identified 23 loci for atrial fibrillation (AF), but the mechanisms responsible for these associations, as well as the causal genes and genetic variants, remain undefined. Methods: To identify the effect of common genetic variants on gene expression that might explain the mechanisms linking genome-wide association loci with AF risk, we performed RNA sequencing of left atrial appendages from a biracial cohort of 265 subjects. Results: Combining gene expression data with genome-wide single nucleotide polymorphism data, we found that approximately two-thirds of the expressed genes were regulated in cis by common genetic variants at a false discovery rate of <0.05, defined as cis-expression quantitative trait loci. Twelve of 23 reported AF genome-wide association loci displayed genome-wide significant cis -expression quantitative trait loci, at PRRX1 (chromosome 1q24), SNRNP27 (1q24), CEP68 (2p14), FKBP7 (2q31), KCNN2 (5q22), FAM13B (5q31), CAV1 (7q31), ASAH1 (8p22), MYOZ1 (10q22), C11ORF45 (11q24), TBX5 (12q24), and SYNE2 (14q23), suggesting that altered expression of these genes plays a role in AF susceptibility. Allelic expression imbalance was used as an independent method to characterize the cis-control of gene expression. One thousand two hundred forty-eight of 5153 queried genes had cis -single nucleotide polymorphisms that significantly regulated allelic expression at a false discovery rate of <0.05. Conclusions: We provide a genome-wide catalog of the genetic control of gene expression in human left atrial appendage. These data can be used to confirm the relevance of genome-wide association loci and to direct future functional studies to identify the genes and genetic variants responsible for complex diseases such as AF.
Hsu, J., Gore-Panter, S., Tchou, G., Castel, L., Lovano, B., Moravec, C. S., Pettersson, G. B., Roselli, E. E., Gillinov, A. M., McCurry, K. R., Smedira, N. G., Barnard, J., Van Wagoner, D. R., Chung, M. K., Smith, J. D.
American Heart Association (AHA)
1942-325X
1942325X
1942-3268
19423268
shingle_catch_all_4 Genetic Control of Left Atrial Gene Expression Yields Insights into the Genetic Susceptibility for Atrial Fibrillation [Original Articles]
Arrhythmias, Gene Expression & Regulation, Functional Genomics
Background: Genome-wide association studies have identified 23 loci for atrial fibrillation (AF), but the mechanisms responsible for these associations, as well as the causal genes and genetic variants, remain undefined. Methods: To identify the effect of common genetic variants on gene expression that might explain the mechanisms linking genome-wide association loci with AF risk, we performed RNA sequencing of left atrial appendages from a biracial cohort of 265 subjects. Results: Combining gene expression data with genome-wide single nucleotide polymorphism data, we found that approximately two-thirds of the expressed genes were regulated in cis by common genetic variants at a false discovery rate of <0.05, defined as cis-expression quantitative trait loci. Twelve of 23 reported AF genome-wide association loci displayed genome-wide significant cis -expression quantitative trait loci, at PRRX1 (chromosome 1q24), SNRNP27 (1q24), CEP68 (2p14), FKBP7 (2q31), KCNN2 (5q22), FAM13B (5q31), CAV1 (7q31), ASAH1 (8p22), MYOZ1 (10q22), C11ORF45 (11q24), TBX5 (12q24), and SYNE2 (14q23), suggesting that altered expression of these genes plays a role in AF susceptibility. Allelic expression imbalance was used as an independent method to characterize the cis-control of gene expression. One thousand two hundred forty-eight of 5153 queried genes had cis -single nucleotide polymorphisms that significantly regulated allelic expression at a false discovery rate of <0.05. Conclusions: We provide a genome-wide catalog of the genetic control of gene expression in human left atrial appendage. These data can be used to confirm the relevance of genome-wide association loci and to direct future functional studies to identify the genes and genetic variants responsible for complex diseases such as AF.
Hsu, J., Gore-Panter, S., Tchou, G., Castel, L., Lovano, B., Moravec, C. S., Pettersson, G. B., Roselli, E. E., Gillinov, A. M., McCurry, K. R., Smedira, N. G., Barnard, J., Van Wagoner, D. R., Chung, M. K., Smith, J. D.
American Heart Association (AHA)
1942-325X
1942325X
1942-3268
19423268
shingle_title_1 Genetic Control of Left Atrial Gene Expression Yields Insights into the Genetic Susceptibility for Atrial Fibrillation [Original Articles]
shingle_title_2 Genetic Control of Left Atrial Gene Expression Yields Insights into the Genetic Susceptibility for Atrial Fibrillation [Original Articles]
shingle_title_3 Genetic Control of Left Atrial Gene Expression Yields Insights into the Genetic Susceptibility for Atrial Fibrillation [Original Articles]
shingle_title_4 Genetic Control of Left Atrial Gene Expression Yields Insights into the Genetic Susceptibility for Atrial Fibrillation [Original Articles]
timestamp 2025-06-30T23:33:35.037Z
titel Genetic Control of Left Atrial Gene Expression Yields Insights into the Genetic Susceptibility for Atrial Fibrillation [Original Articles]
titel_suche Genetic Control of Left Atrial Gene Expression Yields Insights into the Genetic Susceptibility for Atrial Fibrillation [Original Articles]
topic WW-YZ
uid ipn_articles_6208012