Identification of a pleiotropic locus on chromosome 7q for a composite left ventricular wall thickness factor and body mass index: The HyperGEN Study

Weihong Tang, Richard B. Devereux, Na Li, Albert Oberman, Dalane W. Kitzman, Dabeeru C. Rao, Paul N. Hopkins, Steven A. Claas, Donna K. Arnett

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9 Scopus citations


Background: Left ventricular (LV) mass and wall thickness are closely associated with measures of body size and blood pressure and also correlated with systolic and diastolic function, suggesting a contribution of common physiologic mechanisms, including pleiotropic genes, to their covariation. Methods: Doppler echocardiography was performed in 434 African-American (1344 individuals) and 284 white families (1119 individuals). We conducted a genome-wide linkage scan for LV mass, LV structure and function, and composite factors derived from a factor analysis of LV structure and function in the HyperGEN Study population. Results: Factor analysis identified (i) a LV wall thickness factor correlated strongly with interventricular septal thickness (IVSTd) and posterior wall thickness (PWTd) and (ii) a LV diastolic filling factor strongly correlated with early and atrial phase peak transmitral filling velocities. The LV phenotypes and composite factor scores were analyzed in multipoint variance components linkage model implemented in SOLAR with 387 microsatellite markers. In whites, the two highest LODs were 3.42 for LV atrial phase peak filling velocity at 144 cM on chromosome 1 and 3.12 for the LV wall thickness factor at 160 cM on chromosome 7. The peak LODs of the component traits (IVSTd and PWTd) clustered at the same region as the composite factor. Adjusting the factor score for body mass index (BMI) substantially reduced the peak LOD at this region (LOD = 1.92). Bivariate linkage analysis of the composite factor with BMI improved LOD to 3.42 at 158 cM. Also in whites, suggestive linkage was observed on chromosomes 2 and 4 for LV mass, chromosomes 3, 5, 10, and 17 for LV atrial phase peak filling velocity, and chromosome 10 for LV diastolic filling factor. In African Americans, suggestive linkage was observed on chromosome 12 for LV mass, chromosome 21 for IVSTd, and chromosome 3 for LV internal diameter at end-diastole. Conclusion: Our study suggests that a region on chromosome 7 contains pleiotropic genes contributing to the variations of both LV wall thickness and BMI in whites.

Original languageEnglish (US)
Article number40
JournalBMC medical genetics
StatePublished - May 9 2009

Bibliographical note

Funding Information:
HyperGEN is one of four Family Blood Pressure Program networks supported by the NHLBI to identify genetic contributions to hypertension [12]. Hypertensive sibships were drawn from population-based cohorts or from the community-at-large. Eligible hypertensive siblings had onset of hypertension by age 60 years and at least one hypertensive sibling who was willing to participate. Hypertension was defined as average systolic blood pressure (SBP) ≥ 140 mm Hg or average diastolic blood pressure (DBP) ≥ 90 mm Hg on at least two different evaluations, or treatment for hypertension. In its second phase, HyperGEN recruited offspring of the hypertensive siblings. The Genetics of Left Ventricular Hypertrophy Study, a study ancillary to HyperGEN, performed echocardiography in four HyperGEN centers (Minneapolis, MN; Salt Lake City, Utah; Forsyth County, NC; and Birmingham, AL). The Institutional Review Board of participating institutions approved the protocol and all participants gave informed consent. Included in the study are 1344 African Americans (913 hypertensive siblings and 431 offspring) and 1119 whites (589 hypertensive siblings and 530 offspring) who had complete data on echocardiography phenotypes and genetic markers.

Funding Information:
We acknowledge the contributions of HyperGEN investigators at the following institutions: University of Utah (Network Coordinating Center, Field Center, Molecular Genetics Lab); Boston University (Field Center); University of Minnesota (Field Center, Biochemistry Lab); Washington University (Data Coordinating Center); University of Alabama at Birmingham (Field Center, Echo Coordinating and Analysis Center); Medical College of Wisconsin (HyperGEN-Genetics of LVH Genotyping Lab); University of North Carolina (Field Center); Weill Medical College of Cornell University (Echo Reading Center). For a complete list of HyperGEN Investigators see http:// This HyperGEN net- work is funded by cooperative agreements (U10) with the National Heart, Lung, and Blood Institute: HL54471, HL54472, HL54473, HL54495, HL54496, HL54497, HL54509, HL54515, and 2 R01 HL55673-12.


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