Heritability and Genetic Linkage of Left Ventricular Mass, Systolic and Diastolic Function in Hypertensive African Americans (From the GENOA Study)


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Abstract

BackgroundMuch of the interindividual variation in left ventricular (LV) structure and function is unexplained by established risk factors and may be due to novel or genetic factors. We used pedigree information from 454 tandem markers across the genome to estimate the heritability and linkage of various echocardiographic measures of LV structure and function in a cohort of African-American hypertensive siblings.MethodsLV mass was calculated according to the American Society of Echocardiography (ASE) simplified cubed equation and indexed to height2.7. Fractional shortening (FS) was calculated as the percent change in the internal diameter between diastole and systole. Ejection fraction (EF) was calculated from ventricular diameters. Peak mitral early and late diastolic filling velocities were measured from the transmitral pulsed Doppler profile. The maximum-likelihood heritability estimate for each phenotype was obtained using a variance components method. Linkage analyses were performed using the multipoint variance components-based approach.ResultsThere was moderate heritability for LV mass index (34%), interventricular septal thickness (29%), diastolic diameter (42%), EF (40%), FS (39%), and mitral early and late diastolic filling velocities (37 and 45%, respectively). The greatest evidence of genetic linkage was observed for LV mass index on chromosome 3 (logarithm of odds (LOD) score = 2.38), LV EF on chromosome 12 (LOD score = 2.39), and mitral E-wave velocity (MVE) on chromosome 19 (LOD score = 2.69).ConclusionsIn this African-American cohort of hypertensive siblings, the greatest evidence for linkage of LV structure and function was on chromosomes 3, 12, and 19.

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