Heritability and genetic linkage of left ventricular mass, systolic and diastolic function in hypertensive African Americans (From the GENOA Study).
BACKGROUND
Much 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.


METHODS
LV mass was calculated according to the American Society of Echocardiography (ASE) simplified cubed equation and indexed to height(2.7). 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.


RESULTS
There 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).


CONCLUSIONS
In this African-American cohort of hypertensive siblings, the greatest evidence for linkage of LV structure and function was on chromosomes 3, 12, and 19.
Fox
Ervin R
ER
Department of Medicine, University of Mississippi School of Medicine, Jackson, USA. efox@medicine.umsmed.edu
Klos
Kathy L
KL
Penman
Alan D
AD
Blair
George J
GJ
Blossom
Benjamin D
BD
Arnett
Donna
D
Devereux
Richard B
RB
Samdarshi
Tandaw
T
Boerwinkle
Eric
E
Mosley
Thomas H
TH
D001741:Black or African American / Q000235:genetics*; D000368:Aged; D015331:Cohort Studies; D003971:Diastole / Q000235:genetics*; D004452:Echocardiography; D005260:Female; D008040:Genetic Linkage; D006352:Heart Ventricles / Q000033:anatomy & histology* / Q000000981:diagnostic imaging; D006801:Humans; D006973:Hypertension / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D017379:Hypertrophy, Left Ventricular / Q000235:genetics; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D013599:Systole / Q000235:genetics*; D016277:Ventricular Function, Left / Q000235:genetics
Am J Med Sci. 1999 Mar;317(3):168-75
10100690
Am J Hum Genet. 1998 May;62(5):1198-211
9545414
Am J Hypertens. 2002 Jul;15(7 Pt 1):621-7
12118910
J Am Soc Echocardiogr. 2005 Dec;18(12):1440-63
16376782
Hypertension. 2001 Oct;38(4):767-72
11641284
Nat Genet. 1995 Nov;11(3):241-7
7581446
FASEB J. 2006 Jun;20(8):1197-9
16627625
Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14478-83
11121050
J Immunol Methods. 2001 Apr;250(1-2):45-66
11251221
Am Heart J. 2006 Oct;152(4):749-55
16996852
Am J Epidemiol. 1989 Apr;129(4):687-702
2646917
Am J Hypertens. 2003 Feb;16(2):154-7
12559685
N Engl J Med. 1990 May 31;322(22):1561-6
2139921
Am J Cardiol. 2007 May 15;99(10):1413-20
17493471
Hypertension. 2002 Sep;40(3):233-8
12215459
Hypertension. 2007 May;49(5):992-9
17339538
Br J Pharmacol. 2008 Mar;153 Suppl 1:S137-53
18204489
Circ Res. 2000 May 26;86(10):1019-23
10827130
Genomics. 1992 Jul;13(3):829-31
1386340
Ann Intern Med. 1991 Mar 1;114(5):345-52
1825164
Nat Genet. 2002 Jan;30(1):97-101
11731797
Eur Heart J. 2003 Mar;24(6):577-82
12643891
Circ Res. 2006 Mar 17;98(5):596-605
16543510
Am J Med. 2004 May 15;116(10):676-81
15121494
Hypertension. 2002 Jan;39(1):3-9
11799070