TY - JOUR
T1 - Genetic and environmental sources of QT interval variability in Israeli families
T2 - The kibbutz settlements family study
AU - Friedlander, Yechiel
AU - Lapidos, Tyrone
AU - Sinnreich, Ronit
AU - Kark, Jeremy D.
PY - 1999
Y1 - 1999
N2 - QT interval prolongation not attributed to long QT syndromes is reported to be associated with increased risk of sudden and nonsudden cardiac death. Genetic and environmental determinants of QT(c) interval were investigated in an unselected free living population sample of 80 kindreds residing in kibbutz settlements in Israel. The sample included 214 males and 227 females aged 15-97 years. There was a significant familial aggregation of adjusted QT interval levels, as indicated by inter- and intraclass correlation coefficients significantly different from zero. Complex segregation analysis applied to the sex- and age-adjusted data was not conclusive and heterogeneous etiologies for individual differences were suggested. There was evidence for a single recessive locus (q = 0.173) with a major effect in addition to polygenic effects (h2 = 0.41) that explained the mixture of distributions. In parallel, a nontransmitted environmental major factor in addition to polygenic effects that explained the adjusted variation in QT(c) could not be rejected. Similar results were obtained upon the adjustment for sex, age, and environmental covariables. The major factor, either genetic or environmental, and polygenic-loci accounted for about 20 and 33%, of the adjusted QT(c) variation, respectively. Furthermore, sex, age, measured environmental covariables, the unmeasured major factor, and the unmeasured polygenes could account for 63% of the variation of QT(c) in these families. Our data provide evidence for a major factor, either genetic or environmental, in addition to a polygenic background, influencing QT interval levels in a population-based sample of pedigrees.
AB - QT interval prolongation not attributed to long QT syndromes is reported to be associated with increased risk of sudden and nonsudden cardiac death. Genetic and environmental determinants of QT(c) interval were investigated in an unselected free living population sample of 80 kindreds residing in kibbutz settlements in Israel. The sample included 214 males and 227 females aged 15-97 years. There was a significant familial aggregation of adjusted QT interval levels, as indicated by inter- and intraclass correlation coefficients significantly different from zero. Complex segregation analysis applied to the sex- and age-adjusted data was not conclusive and heterogeneous etiologies for individual differences were suggested. There was evidence for a single recessive locus (q = 0.173) with a major effect in addition to polygenic effects (h2 = 0.41) that explained the mixture of distributions. In parallel, a nontransmitted environmental major factor in addition to polygenic effects that explained the adjusted variation in QT(c) could not be rejected. Similar results were obtained upon the adjustment for sex, age, and environmental covariables. The major factor, either genetic or environmental, and polygenic-loci accounted for about 20 and 33%, of the adjusted QT(c) variation, respectively. Furthermore, sex, age, measured environmental covariables, the unmeasured major factor, and the unmeasured polygenes could account for 63% of the variation of QT(c) in these families. Our data provide evidence for a major factor, either genetic or environmental, in addition to a polygenic background, influencing QT interval levels in a population-based sample of pedigrees.
KW - Genetics
KW - Heritability
KW - Major gene
KW - QT interval
UR - http://www.scopus.com/inward/record.url?scp=0032725330&partnerID=8YFLogxK
U2 - 10.1034/j.1399-0004.1999.560304.x
DO - 10.1034/j.1399-0004.1999.560304.x
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C2 - 10563479
AN - SCOPUS:0032725330
SN - 0009-9163
VL - 56
SP - 200
EP - 209
JO - Clinical Genetics
JF - Clinical Genetics
IS - 3
ER -