Familial aggregation of QT-interval variability in a general population: results from the NHLBI Family Heart Study

QT-interval prolongation is associated with increased risk of cardiac death , Although information on genetics and molecular mechanisms of the congenit al long QT syndrome is mounting, limited data are available on the genetics of QT interval in the general population. Heart rate adjusted QT intervals (Bazett's QTc, and QT index (QTI)) were assessed by electrocardiography in 2399 members aged 25-91 years of 468 randomly selected families participat ing in the NHLBI Family Heart Study, Familial correlation and segregation a nalyses were performed to evaluate the genetics of the variability of QT in terval in this population. The parent-offspring (0.14 +/- 0.03) and sibling (0.18 +/- 0.03) correlations for age and sex-adjusted QTc were moderate, w hile the spouse correlation was close to zero (0.09 +/- 0.06). This suggest s that there are familial/genetic influences on QT-interval variability. Se gregation analysis results suggest that there is a major effect in addition to heritable multifactorial effects (h(2) = 0.34), but the major effect di d not follow Mendelian inheritance. Further adjustments of QTc for other ma jor cardiovascular risk factors did not significantly change the results, S imilar results were found for QTI. The QT-interval variation in the general population is influenced by modera te heritable multifactorial effects in addition to a major effect. A major gene effect is not directly supported.