Dataset Information

A comprehensive genetic study on left atrium size in Caribbean Hispanics identifies potential candidate genes in 17p10.

ABSTRACT: 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.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 (h(2)=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).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.

SUBMITTER: Wang L

PROVIDER: S-EPMC2923674 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A comprehensive genetic study on left atrium size in Caribbean Hispanics identifies potential candidate genes in 17p10.

Wang Liyong L Di Tullio Marco R MR Beecham Ashley A Slifer Susan S Rundek Tatjana T Homma Shunichi S Blanton Susan H SH Sacco Ralph L RL

Circulation. Cardiovascular genetics 20100619 4

<h4>Background</h4>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.<h4>Methods and results</h4>One hundred Dominican families comprising 1350 individuals were studied to estimate heritability and map quantitative trait loci for L ...[more]

PMID: 20562446

Similar Datasets

Project description:Existing algorithms account for ~50% of observed variance in warfarin dose requirements after including common polymorphisms. However, they do not perform as well in populations other than Caucasians, in part because some ethno-specific genetic variants are overlooked. The objective of the present study was to identify genetic polymorphisms that can explain variability in warfarin dose requirements among Caribbean Hispanics of Puerto Rico. Next-Generation Sequencing of candidate genes CYP2C9 and VKORC1 and genotyping by DMET® Plus Assay of cardiovascular patients were performed. We also aimed at characterizing the genomic structure and admixture pattern of this study cohort. Our study used the Extreme Discordant Phenotype approach to perform a case-control association analysis. The CYP2C9 variant rs2860905, which was found in all the major haplotypes occurring in the Puerto Rican population, showed stronger association with warfarin sensitivity (<4 mg/day) than common variants CYP2C9*2 and CYP2C9*3. Although, CYP2C9*2 and CYP2C9*3 are separately contained within two of the haplotypes, 10 subjects with the sensitive phenotype were carriers of only the CYP2C9 rs2860905 variant. Other polymorphisms in CES2 and ABCB1 were found to be associated with warfarin resistance. Incorporation of rs2860905 in a regression model (R2 = 0.63, MSE = 0.37) that also includes additional genetics (i.e., VKORC1-1639 G>A; CYP2C9 rs1856908; ABCB1 c.IVS9-44A>G/ rs10276036; CES2 c.269-965A>G/ rs4783745) and non-genetic factors (i.e., hypertension, diabetes and age) showed better prediction of warfarin dose requirements than CYP2C9*2 and CYP2C9*3 combined (partial R2 = 0.132 vs. 0.023 and 0.007, respectively, p < 0.001). The genetic background of Puerto Ricans in the study cohort showed a tri-hybrid admixture pattern, with a slightly higher than expected contribution of Native American ancestry (25%). The genomic diversity of Puerto Ricans is highlighted by the presence of four different major haplotype blocks in the CYP2C9 locus. Although, our findings need further replication, this study contributes to the field by identifying novel genetic variants that increase predictability of stable warfarin dosing among Caribbean Hispanics.

Dataset Information

A comprehensive genetic study on left atrium size in Caribbean Hispanics identifies potential candidate genes in 17p10.

Publications

A comprehensive genetic study on left atrium size in Caribbean Hispanics identifies potential candidate genes in 17p10.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets