Novel quantitative trait locus is mapped to chromosome 12p11 for left ventricular mass in Dominican families: The Family Study of Stroke Risk and Carotid Atherosclerosis

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

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5 Citations (Scopus)

Abstract

Background: Left ventricular mass (LVM) is an important risk factor for stroke and vascular disease. The genetic basis of LVM is unclear although a high heritability has been suggested. We sought to map quantitative trait loci (QTL) for LVM using large Dominican families. Methods: Probands were selected from Dominican subjects of the population-based Northern Manhattan Study (NOMAS). LVM was measured by transthoracic echocardiography. A set of 405 microsatellite markers was used to screen the whole genome among 1360 subjects from 100 Dominican families who had complete phenotype data and DNA available. A polygenic covariate screening was run to identify the significant covariates. Variance components analysis was used to estimate heritability and to detect evidence for linkage, after adjusting for significant risk factors. Ordered-subset Analysis (OSA) was conducted to identify a more homogeneous subset for stratification analysis. Results: LVM had a heritability of 0.58 in the studied population (p < 0.0001). The most significant evidence for linkage was found at chromosome 12p11 (MLOD = 3.11, empirical p = 0.0003) with peak marker at D12S1042. This linkage was significantly increased in a subset of families with the high average waist circumference (MLOD = 4.45, p = 0.0045 for increase in evidence for linkage). Conclusion: We mapped a novel QTL near D12S1042 for LVM in Dominicans. Enhanced linkage evidence in families with larger waist circumference suggests that gene(s) residing within the QTL interact(s) with abdominal obesity to contribute to phenotypic variation of LVM. Suggestive evidence for linkage (LOD = 1.99) has been reported at the same peak marker for left ventricular geometry in a White population from the HyperGEN study, underscoring the importance of this QTL for left ventricular phenotype. Further fine mapping and validation studies are warranted to identify the underpinning genes.

Original languageEnglish
Article number74
JournalBMC Medical Genetics
Volume10
DOIs
StatePublished - Jul 23 2009

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Carotid Artery Diseases
Quantitative Trait Loci
Chromosomes
Stroke
Waist Circumference
Population
Phenotype
Abdominal Obesity
Validation Studies
Vascular Diseases
Microsatellite Repeats
Genes
Echocardiography
Analysis of Variance
Genome
DNA

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

@article{2be004e6d6634edcacf3760641199d6a,
title = "Novel quantitative trait locus is mapped to chromosome 12p11 for left ventricular mass in Dominican families: The Family Study of Stroke Risk and Carotid Atherosclerosis",
abstract = "Background: Left ventricular mass (LVM) is an important risk factor for stroke and vascular disease. The genetic basis of LVM is unclear although a high heritability has been suggested. We sought to map quantitative trait loci (QTL) for LVM using large Dominican families. Methods: Probands were selected from Dominican subjects of the population-based Northern Manhattan Study (NOMAS). LVM was measured by transthoracic echocardiography. A set of 405 microsatellite markers was used to screen the whole genome among 1360 subjects from 100 Dominican families who had complete phenotype data and DNA available. A polygenic covariate screening was run to identify the significant covariates. Variance components analysis was used to estimate heritability and to detect evidence for linkage, after adjusting for significant risk factors. Ordered-subset Analysis (OSA) was conducted to identify a more homogeneous subset for stratification analysis. Results: LVM had a heritability of 0.58 in the studied population (p < 0.0001). The most significant evidence for linkage was found at chromosome 12p11 (MLOD = 3.11, empirical p = 0.0003) with peak marker at D12S1042. This linkage was significantly increased in a subset of families with the high average waist circumference (MLOD = 4.45, p = 0.0045 for increase in evidence for linkage). Conclusion: We mapped a novel QTL near D12S1042 for LVM in Dominicans. Enhanced linkage evidence in families with larger waist circumference suggests that gene(s) residing within the QTL interact(s) with abdominal obesity to contribute to phenotypic variation of LVM. Suggestive evidence for linkage (LOD = 1.99) has been reported at the same peak marker for left ventricular geometry in a White population from the HyperGEN study, underscoring the importance of this QTL for left ventricular phenotype. Further fine mapping and validation studies are warranted to identify the underpinning genes.",
author = "Liyong Wang and Ashley Beecham and {Di Tullio}, {Marco R.} and Susan Slifer and Blanton, {Susan H} and Tatjana Rundek and Sacco, {Ralph L}",
year = "2009",
month = "7",
day = "23",
doi = "10.1186/1471-2350-10-74",
language = "English",
volume = "10",
journal = "BMC Medical Genetics",
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TY - JOUR

T1 - Novel quantitative trait locus is mapped to chromosome 12p11 for left ventricular mass in Dominican families

T2 - The Family Study of Stroke Risk and Carotid Atherosclerosis

AU - Wang, Liyong

AU - Beecham, Ashley

AU - Di Tullio, Marco R.

AU - Slifer, Susan

AU - Blanton, Susan H

AU - Rundek, Tatjana

AU - Sacco, Ralph L

PY - 2009/7/23

Y1 - 2009/7/23

N2 - Background: Left ventricular mass (LVM) is an important risk factor for stroke and vascular disease. The genetic basis of LVM is unclear although a high heritability has been suggested. We sought to map quantitative trait loci (QTL) for LVM using large Dominican families. Methods: Probands were selected from Dominican subjects of the population-based Northern Manhattan Study (NOMAS). LVM was measured by transthoracic echocardiography. A set of 405 microsatellite markers was used to screen the whole genome among 1360 subjects from 100 Dominican families who had complete phenotype data and DNA available. A polygenic covariate screening was run to identify the significant covariates. Variance components analysis was used to estimate heritability and to detect evidence for linkage, after adjusting for significant risk factors. Ordered-subset Analysis (OSA) was conducted to identify a more homogeneous subset for stratification analysis. Results: LVM had a heritability of 0.58 in the studied population (p < 0.0001). The most significant evidence for linkage was found at chromosome 12p11 (MLOD = 3.11, empirical p = 0.0003) with peak marker at D12S1042. This linkage was significantly increased in a subset of families with the high average waist circumference (MLOD = 4.45, p = 0.0045 for increase in evidence for linkage). Conclusion: We mapped a novel QTL near D12S1042 for LVM in Dominicans. Enhanced linkage evidence in families with larger waist circumference suggests that gene(s) residing within the QTL interact(s) with abdominal obesity to contribute to phenotypic variation of LVM. Suggestive evidence for linkage (LOD = 1.99) has been reported at the same peak marker for left ventricular geometry in a White population from the HyperGEN study, underscoring the importance of this QTL for left ventricular phenotype. Further fine mapping and validation studies are warranted to identify the underpinning genes.

AB - Background: Left ventricular mass (LVM) is an important risk factor for stroke and vascular disease. The genetic basis of LVM is unclear although a high heritability has been suggested. We sought to map quantitative trait loci (QTL) for LVM using large Dominican families. Methods: Probands were selected from Dominican subjects of the population-based Northern Manhattan Study (NOMAS). LVM was measured by transthoracic echocardiography. A set of 405 microsatellite markers was used to screen the whole genome among 1360 subjects from 100 Dominican families who had complete phenotype data and DNA available. A polygenic covariate screening was run to identify the significant covariates. Variance components analysis was used to estimate heritability and to detect evidence for linkage, after adjusting for significant risk factors. Ordered-subset Analysis (OSA) was conducted to identify a more homogeneous subset for stratification analysis. Results: LVM had a heritability of 0.58 in the studied population (p < 0.0001). The most significant evidence for linkage was found at chromosome 12p11 (MLOD = 3.11, empirical p = 0.0003) with peak marker at D12S1042. This linkage was significantly increased in a subset of families with the high average waist circumference (MLOD = 4.45, p = 0.0045 for increase in evidence for linkage). Conclusion: We mapped a novel QTL near D12S1042 for LVM in Dominicans. Enhanced linkage evidence in families with larger waist circumference suggests that gene(s) residing within the QTL interact(s) with abdominal obesity to contribute to phenotypic variation of LVM. Suggestive evidence for linkage (LOD = 1.99) has been reported at the same peak marker for left ventricular geometry in a White population from the HyperGEN study, underscoring the importance of this QTL for left ventricular phenotype. Further fine mapping and validation studies are warranted to identify the underpinning genes.

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