A comprehensive Genetic Study on left atrium size in Caribbean Hispanics Identifies potential candidate genes in 17p10

Liyong Wang, Marco R Di Tullio, Ashley Beecham, Susan Slifer, Tatjana Rundek, Shunichi Homma, Susan H Blanton, Ralph L Sacco

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background-Left atrial (LA) enlargement is associated with cardiovascular disease and stroke. Genetic factors contributing to the LA dimension are poorly understood. We sought to map susceptibility genes for LA size in a large Dominican family data set and an independent population-based sample from the Northern Manhattan Study. Methods and Results-One hundred Dominican families comprising 1350 individuals were studied to estimate heritability and map quantitative trait loci for LA size using variance components analysis. LA dimension was measured by transthoracic echocardiography. A polygenic covariate screening was used to identify significant covariates. LA size had a moderate estimate of heritability (h2=0.42) after adjusting for significant covariates. Linkage analysis revealed suggestive evidence on chromosome 10p19 (D10S1423, MLOD=2.00) and 17p10 (D17S974, MLOD=2.05). Ordered subset analysis found significantly enhanced (P<0.05 for increase of LOD score) evidence for linkage at 17p10 (MLOD=2.9) in families with lower LDL level. Single nucleotide polymophisms (n=2233)were used to perform a peak-wide association mapping across 17p10 in 825 NOMAS individuals. Evidence for association were found in NTN1, MYH10, COX10, and MYOCD genes (P=0.00005 to 0.005). Conclusions-Using nonbiased genome-wide linkage followed by peak-wide association analysis, we identified several possible susceptibility genes affecting LA size. Among them, MYOCD has been shown to serve as a key transducer of hypertrophic signals in cardiomyocytes. Our data support that polymorphisms in MYOCD modify LA size.

Original languageEnglish
Pages (from-to)386-392
Number of pages7
JournalCirculation: Cardiovascular Genetics
Volume3
Issue number4
DOIs
StatePublished - Aug 1 2010

Fingerprint

Heart Atria
Hispanic Americans
Genes
Quantitative Trait Loci
Transducers
Cardiac Myocytes
Echocardiography
Analysis of Variance
Cardiovascular Diseases
Nucleotides
Chromosomes
Myocardial Infarction
Genome
Population

Keywords

  • COX10
  • Genetics
  • Left atrium
  • MYH10
  • Myocardin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)
  • Genetics

Cite this

A comprehensive Genetic Study on left atrium size in Caribbean Hispanics Identifies potential candidate genes in 17p10. / Wang, Liyong; Tullio, Marco R Di; Beecham, Ashley; Slifer, Susan; Rundek, Tatjana; Homma, Shunichi; Blanton, Susan H; Sacco, Ralph L.

In: Circulation: Cardiovascular Genetics, Vol. 3, No. 4, 01.08.2010, p. 386-392.

Research output: Contribution to journalArticle

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abstract = "Background-Left atrial (LA) enlargement is associated with cardiovascular disease and stroke. Genetic factors contributing to the LA dimension are poorly understood. We sought to map susceptibility genes for LA size in a large Dominican family data set and an independent population-based sample from the Northern Manhattan Study. Methods and Results-One hundred Dominican families comprising 1350 individuals were studied to estimate heritability and map quantitative trait loci for LA size using variance components analysis. LA dimension was measured by transthoracic echocardiography. A polygenic covariate screening was used to identify significant covariates. LA size had a moderate estimate of heritability (h2=0.42) after adjusting for significant covariates. Linkage analysis revealed suggestive evidence on chromosome 10p19 (D10S1423, MLOD=2.00) and 17p10 (D17S974, MLOD=2.05). Ordered subset analysis found significantly enhanced (P<0.05 for increase of LOD score) evidence for linkage at 17p10 (MLOD=2.9) in families with lower LDL level. Single nucleotide polymophisms (n=2233)were used to perform a peak-wide association mapping across 17p10 in 825 NOMAS individuals. Evidence for association were found in NTN1, MYH10, COX10, and MYOCD genes (P=0.00005 to 0.005). Conclusions-Using nonbiased genome-wide linkage followed by peak-wide association analysis, we identified several possible susceptibility genes affecting LA size. Among them, MYOCD has been shown to serve as a key transducer of hypertrophic signals in cardiomyocytes. Our data support that polymorphisms in MYOCD modify LA size.",
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AB - Background-Left atrial (LA) enlargement is associated with cardiovascular disease and stroke. Genetic factors contributing to the LA dimension are poorly understood. We sought to map susceptibility genes for LA size in a large Dominican family data set and an independent population-based sample from the Northern Manhattan Study. Methods and Results-One hundred Dominican families comprising 1350 individuals were studied to estimate heritability and map quantitative trait loci for LA size using variance components analysis. LA dimension was measured by transthoracic echocardiography. A polygenic covariate screening was used to identify significant covariates. LA size had a moderate estimate of heritability (h2=0.42) after adjusting for significant covariates. Linkage analysis revealed suggestive evidence on chromosome 10p19 (D10S1423, MLOD=2.00) and 17p10 (D17S974, MLOD=2.05). Ordered subset analysis found significantly enhanced (P<0.05 for increase of LOD score) evidence for linkage at 17p10 (MLOD=2.9) in families with lower LDL level. Single nucleotide polymophisms (n=2233)were used to perform a peak-wide association mapping across 17p10 in 825 NOMAS individuals. Evidence for association were found in NTN1, MYH10, COX10, and MYOCD genes (P=0.00005 to 0.005). Conclusions-Using nonbiased genome-wide linkage followed by peak-wide association analysis, we identified several possible susceptibility genes affecting LA size. Among them, MYOCD has been shown to serve as a key transducer of hypertrophic signals in cardiomyocytes. Our data support that polymorphisms in MYOCD modify LA size.

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