Genetic association analysis of the cardiovascular biomarker: N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP)
NT-proBNP is a biomarker of cardiovascular disease (CVD). Little is known about the heritability and genetic variants associated with NT-proBNP. Therefore, we estimated the heritability of and examined genetic associations of SNPs in the BNP gene region with circulating NT-proBNP and prevalent CVD i...
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| Published in | PloS one Vol. 16; no. 3; p. e0248726 |
|---|---|
| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Public Library of Science
15.03.2021
Public Library of Science (PLoS) |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1932-6203 1932-6203 |
| DOI | 10.1371/journal.pone.0248726 |
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| Abstract | NT-proBNP is a biomarker of cardiovascular disease (CVD). Little is known about the heritability and genetic variants associated with NT-proBNP. Therefore, we estimated the heritability of and examined genetic associations of SNPs in the BNP gene region with circulating NT-proBNP and prevalent CVD in 4,331 participants from the Long Life Family Study (LLFS).
Genotypes of 10 SNPs from the NPPB and NPPA regions that encode BNP and A-type natriuretic peptide, respectively, were tested for association with NT-proBNP and prevalent cardiovascular disease and risk factors. We performed analyses using the Sequential Oligogenic Linkage Analysis (SOLAR) program to account for family relatedness, and adjusted all models for age, sex, and field center. The mean age of the LLFS was 69.8 years (range 24-110) with 55.4% females. NT-proBNP was significantly heritable (h2 = 0.21; P = 4x10-14), and the minor alleles of rs632793 (p<0.001) and rs41300100 (p = 0.05) were independently associated with higher serum NT-proBNP levels. Additionally, the minor allele of rs632793 was significantly and consistently associated with lower prevalent CVD, including blood pressures, independent of NT-proBNP level (all P<0.05). Results for prevalent CVD, but not NT-proBNP levels, showed significant interaction by familial generation.
In this family-based study of subjects with exceptional longevity, we identified several allelic variants in the BNP gene region associated with NT-pro-BNP levels and prevalent CVD. |
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| AbstractList | NT-proBNP is a biomarker of cardiovascular disease (CVD). Little is known about the heritability and genetic variants associated with NT-proBNP. Therefore, we estimated the heritability of and examined genetic associations of SNPs in the BNP gene region with circulating NT-proBNP and prevalent CVD in 4,331 participants from the Long Life Family Study (LLFS). Genotypes of 10 SNPs from the NPPB and NPPA regions that encode BNP and A-type natriuretic peptide, respectively, were tested for association with NT-proBNP and prevalent cardiovascular disease and risk factors. We performed analyses using the Sequential Oligogenic Linkage Analysis (SOLAR) program to account for family relatedness, and adjusted all models for age, sex, and field center. The mean age of the LLFS was 69.8 years (range 24-110) with 55.4% females. NT-proBNP was significantly heritable (h.sup.2 = 0.21; P = 4x10.sup.-14 ), and the minor alleles of rs632793 (p<0.001) and rs41300100 (p = 0.05) were independently associated with higher serum NT-proBNP levels. Additionally, the minor allele of rs632793 was significantly and consistently associated with lower prevalent CVD, including blood pressures, independent of NT-proBNP level (all P<0.05). Results for prevalent CVD, but not NT-proBNP levels, showed significant interaction by familial generation. In this family-based study of subjects with exceptional longevity, we identified several allelic variants in the BNP gene region associated with NT-pro-BNP levels and prevalent CVD. Background NT-proBNP is a biomarker of cardiovascular disease (CVD). Little is known about the heritability and genetic variants associated with NT-proBNP. Therefore, we estimated the heritability of and examined genetic associations of SNPs in the BNP gene region with circulating NT-proBNP and prevalent CVD in 4,331 participants from the Long Life Family Study (LLFS). Methods and results Genotypes of 10 SNPs from the NPPB and NPPA regions that encode BNP and A-type natriuretic peptide, respectively, were tested for association with NT-proBNP and prevalent cardiovascular disease and risk factors. We performed analyses using the Sequential Oligogenic Linkage Analysis (SOLAR) program to account for family relatedness, and adjusted all models for age, sex, and field center. The mean age of the LLFS was 69.8 years (range 24-110) with 55.4% females. NT-proBNP was significantly heritable (h.sup.2 = 0.21; P = 4x10.sup.-14 ), and the minor alleles of rs632793 (p<0.001) and rs41300100 (p = 0.05) were independently associated with higher serum NT-proBNP levels. Additionally, the minor allele of rs632793 was significantly and consistently associated with lower prevalent CVD, including blood pressures, independent of NT-proBNP level (all P<0.05). Results for prevalent CVD, but not NT-proBNP levels, showed significant interaction by familial generation. Conclusion In this family-based study of subjects with exceptional longevity, we identified several allelic variants in the BNP gene region associated with NT-pro-BNP levels and prevalent CVD. NT-proBNP is a biomarker of cardiovascular disease (CVD). Little is known about the heritability and genetic variants associated with NT-proBNP. Therefore, we estimated the heritability of and examined genetic associations of SNPs in the BNP gene region with circulating NT-proBNP and prevalent CVD in 4,331 participants from the Long Life Family Study (LLFS).BACKGROUNDNT-proBNP is a biomarker of cardiovascular disease (CVD). Little is known about the heritability and genetic variants associated with NT-proBNP. Therefore, we estimated the heritability of and examined genetic associations of SNPs in the BNP gene region with circulating NT-proBNP and prevalent CVD in 4,331 participants from the Long Life Family Study (LLFS).Genotypes of 10 SNPs from the NPPB and NPPA regions that encode BNP and A-type natriuretic peptide, respectively, were tested for association with NT-proBNP and prevalent cardiovascular disease and risk factors. We performed analyses using the Sequential Oligogenic Linkage Analysis (SOLAR) program to account for family relatedness, and adjusted all models for age, sex, and field center. The mean age of the LLFS was 69.8 years (range 24-110) with 55.4% females. NT-proBNP was significantly heritable (h2 = 0.21; P = 4x10-14), and the minor alleles of rs632793 (p<0.001) and rs41300100 (p = 0.05) were independently associated with higher serum NT-proBNP levels. Additionally, the minor allele of rs632793 was significantly and consistently associated with lower prevalent CVD, including blood pressures, independent of NT-proBNP level (all P<0.05). Results for prevalent CVD, but not NT-proBNP levels, showed significant interaction by familial generation.METHODS AND RESULTSGenotypes of 10 SNPs from the NPPB and NPPA regions that encode BNP and A-type natriuretic peptide, respectively, were tested for association with NT-proBNP and prevalent cardiovascular disease and risk factors. We performed analyses using the Sequential Oligogenic Linkage Analysis (SOLAR) program to account for family relatedness, and adjusted all models for age, sex, and field center. The mean age of the LLFS was 69.8 years (range 24-110) with 55.4% females. NT-proBNP was significantly heritable (h2 = 0.21; P = 4x10-14), and the minor alleles of rs632793 (p<0.001) and rs41300100 (p = 0.05) were independently associated with higher serum NT-proBNP levels. Additionally, the minor allele of rs632793 was significantly and consistently associated with lower prevalent CVD, including blood pressures, independent of NT-proBNP level (all P<0.05). Results for prevalent CVD, but not NT-proBNP levels, showed significant interaction by familial generation.In this family-based study of subjects with exceptional longevity, we identified several allelic variants in the BNP gene region associated with NT-pro-BNP levels and prevalent CVD.CONCLUSIONIn this family-based study of subjects with exceptional longevity, we identified several allelic variants in the BNP gene region associated with NT-pro-BNP levels and prevalent CVD. BackgroundNT-proBNP is a biomarker of cardiovascular disease (CVD). Little is known about the heritability and genetic variants associated with NT-proBNP. Therefore, we estimated the heritability of and examined genetic associations of SNPs in the BNP gene region with circulating NT-proBNP and prevalent CVD in 4,331 participants from the Long Life Family Study (LLFS).Methods and resultsGenotypes of 10 SNPs from the NPPB and NPPA regions that encode BNP and A-type natriuretic peptide, respectively, were tested for association with NT-proBNP and prevalent cardiovascular disease and risk factors. We performed analyses using the Sequential Oligogenic Linkage Analysis (SOLAR) program to account for family relatedness, and adjusted all models for age, sex, and field center. The mean age of the LLFS was 69.8 years (range 24-110) with 55.4% females. NT-proBNP was significantly heritable (h2 = 0.21; P = 4x10-14), and the minor alleles of rs632793 (p<0.001) and rs41300100 (p = 0.05) were independently associated with higher serum NT-proBNP levels. Additionally, the minor allele of rs632793 was significantly and consistently associated with lower prevalent CVD, including blood pressures, independent of NT-proBNP level (all P<0.05). Results for prevalent CVD, but not NT-proBNP levels, showed significant interaction by familial generation.ConclusionIn this family-based study of subjects with exceptional longevity, we identified several allelic variants in the BNP gene region associated with NT-pro-BNP levels and prevalent CVD. NT-proBNP is a biomarker of cardiovascular disease (CVD). Little is known about the heritability and genetic variants associated with NT-proBNP. Therefore, we estimated the heritability of and examined genetic associations of SNPs in the BNP gene region with circulating NT-proBNP and prevalent CVD in 4,331 participants from the Long Life Family Study (LLFS). Genotypes of 10 SNPs from the NPPB and NPPA regions that encode BNP and A-type natriuretic peptide, respectively, were tested for association with NT-proBNP and prevalent cardiovascular disease and risk factors. We performed analyses using the Sequential Oligogenic Linkage Analysis (SOLAR) program to account for family relatedness, and adjusted all models for age, sex, and field center. The mean age of the LLFS was 69.8 years (range 24-110) with 55.4% females. NT-proBNP was significantly heritable (h2 = 0.21; P = 4x10-14), and the minor alleles of rs632793 (p<0.001) and rs41300100 (p = 0.05) were independently associated with higher serum NT-proBNP levels. Additionally, the minor allele of rs632793 was significantly and consistently associated with lower prevalent CVD, including blood pressures, independent of NT-proBNP level (all P<0.05). Results for prevalent CVD, but not NT-proBNP levels, showed significant interaction by familial generation. In this family-based study of subjects with exceptional longevity, we identified several allelic variants in the BNP gene region associated with NT-pro-BNP levels and prevalent CVD. |
| Audience | Academic |
| Author | Kuipers, Allison L. Thyagarajan, Bharat Yang, Yuan Zmuda, Joseph M. Wojczynski, Mary K. Cvejkus, Ryan K. Christensen, Kaare |
| AuthorAffiliation | 1 Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, United States of America 4 Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, United States of America 5 Department of Epidemiology, Biostatistics and Biodemography, Danish Aging Research Center, University of Southern Denmark, Odense C, Denmark 2 Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, United States of America 3 Department of Genetics, Washington University in St Louis, St. Louis, MO, United States of America University of Texas School of Public Health, UNITED STATES |
| AuthorAffiliation_xml | – name: 1 Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, United States of America – name: 4 Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, United States of America – name: 2 Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, United States of America – name: 3 Department of Genetics, Washington University in St Louis, St. Louis, MO, United States of America – name: 5 Department of Epidemiology, Biostatistics and Biodemography, Danish Aging Research Center, University of Southern Denmark, Odense C, Denmark – name: University of Texas School of Public Health, UNITED STATES |
| Author_xml | – sequence: 1 givenname: Yuan surname: Yang fullname: Yang, Yuan – sequence: 2 givenname: Joseph M. surname: Zmuda fullname: Zmuda, Joseph M. – sequence: 3 givenname: Mary K. surname: Wojczynski fullname: Wojczynski, Mary K. – sequence: 4 givenname: Bharat surname: Thyagarajan fullname: Thyagarajan, Bharat – sequence: 5 givenname: Kaare surname: Christensen fullname: Christensen, Kaare – sequence: 6 givenname: Ryan K. surname: Cvejkus fullname: Cvejkus, Ryan K. – sequence: 7 givenname: Allison L. orcidid: 0000-0003-1415-1742 surname: Kuipers fullname: Kuipers, Allison L. |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33720941$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_1002_biof_1875 crossref_primary_10_15829_1560_4071_2024_5906 crossref_primary_10_2196_37011 |
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| Snippet | NT-proBNP is a biomarker of cardiovascular disease (CVD). Little is known about the heritability and genetic variants associated with NT-proBNP. Therefore, we... Background NT-proBNP is a biomarker of cardiovascular disease (CVD). Little is known about the heritability and genetic variants associated with NT-proBNP.... BackgroundNT-proBNP is a biomarker of cardiovascular disease (CVD). Little is known about the heritability and genetic variants associated with NT-proBNP.... |
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| SubjectTerms | Adult Age Aged Aged, 80 and over Aging Alleles Association analysis Biology and Life Sciences Biomarkers Biomarkers - blood Brain natriuretic peptide Cardiovascular disease Cardiovascular diseases Cardiovascular Diseases - blood Cardiovascular Diseases - genetics Congestive heart failure Coronary artery Coronary artery disease Data analysis Diagnosis Editing Epidemiology Female Funding Genes Genetic analysis Genetic aspects Genetics Genotype & phenotype Health aspects Health risks Heart diseases Heart failure Humans Hypertension Laboratories Male Medical prognosis Medicine and Health Sciences Methodology Middle Aged Natriuretic Peptide, Brain - blood Natriuretic Peptide, Brain - genetics Natriuretic peptides Nucleotides Outliers (statistics) Peptide Fragments - blood Peptide Fragments - genetics Peptides Physiological aspects Polymorphism, Single Nucleotide Population studies Research facilities Risk Factors Single-nucleotide polymorphism |
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| Title | Genetic association analysis of the cardiovascular biomarker: N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) |
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