TY - JOUR
T1 - Genetic and environmental sources of fibrinogen variability in Israeli families
T2 - The Kibbutzim family study
AU - Friedlander, Yechiel
AU - Elkana, Yehudit
AU - Sinnreich, Ronit
AU - Kark, Jeremy D.
PY - 1995/5
Y1 - 1995/5
N2 - Genetic and environmental determinants of plasma fibrinogen were investigated in a sample of 82 kindreds residing in kibbutz settlements in Israel. The sample included 223 males and 229 females ages 15-97 years. Fibrinogen levels were first adjusted for variability in sex and age. There was a significant familial aggregation of adjusted fibrinogen levels, as indicated by inter- and intraclass correlation coefficients significantly different from zero. Commingling analysis implied that in this population a mixture of two normal distributions fit the adjusted fibrinogen levels better than did a single normal distribution. Complex segregation analysis was first applied to these sex- and age-adjusted data. Heterogeneous etiologies for individual differences were suggested. There was evidence for a nontransmitted environmental major factor in addition to polygenic genes that explained the mixture of distributions. In parallel, a single recessive locus with a major effect that explained the adjusted variation in fibrinogen could not be rejected. However, when the regression model for sex and age allowed coefficients to be ousiotype (class)-specific, the recessive genetic model was rejected and the mixed environmental one was not. These results suggested that particular ousiotypes determined by the major environmental factor are associated with a steeper increase of fibrinogen with age. While at the age of 20 years, the major environmental factor contributed 10% to fibrinogen variability, and 48% was explained by polygenic loci, at 80 years of age, the major factor explained 64% and only ~20% was explained by polygenic factors.
AB - Genetic and environmental determinants of plasma fibrinogen were investigated in a sample of 82 kindreds residing in kibbutz settlements in Israel. The sample included 223 males and 229 females ages 15-97 years. Fibrinogen levels were first adjusted for variability in sex and age. There was a significant familial aggregation of adjusted fibrinogen levels, as indicated by inter- and intraclass correlation coefficients significantly different from zero. Commingling analysis implied that in this population a mixture of two normal distributions fit the adjusted fibrinogen levels better than did a single normal distribution. Complex segregation analysis was first applied to these sex- and age-adjusted data. Heterogeneous etiologies for individual differences were suggested. There was evidence for a nontransmitted environmental major factor in addition to polygenic genes that explained the mixture of distributions. In parallel, a single recessive locus with a major effect that explained the adjusted variation in fibrinogen could not be rejected. However, when the regression model for sex and age allowed coefficients to be ousiotype (class)-specific, the recessive genetic model was rejected and the mixed environmental one was not. These results suggested that particular ousiotypes determined by the major environmental factor are associated with a steeper increase of fibrinogen with age. While at the age of 20 years, the major environmental factor contributed 10% to fibrinogen variability, and 48% was explained by polygenic loci, at 80 years of age, the major factor explained 64% and only ~20% was explained by polygenic factors.
UR - http://www.scopus.com/inward/record.url?scp=0028958950&partnerID=8YFLogxK
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 7726177
AN - SCOPUS:0028958950
SN - 0002-9297
VL - 56
SP - 1194
EP - 1206
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 5
ER -