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


RESULTS
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).


CONCLUSIONS
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.
Wang
Liyong
L
John T. McDonald Department of Human Genetics, John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
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
D000328:Adult; D000368:Aged; D017691:Caribbean Region / Q000208:ethnology; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006325:Heart Atria / Q000033:anatomy & histology* / Q000000981:diagnostic imaging; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D009929:Organ Size / Q000235:genetics; D040641:Quantitative Trait Loci; D014463:Ultrasonography