Genetic and environmental sources of fibrinogen variability in Israeli families: the Kibbutzim Family Study.
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 approximately 20% was explained by polygenic factors.
Friedlander
Y
Y
Department of Social Medicine, Hadassah Medical Organization and Hebrew University--Hadassah School of Public Health, Jerusalem, Israel.
Elkana
Y
Y
Sinnreich
R
R
Kark
J D
JD
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D003327:Coronary Disease / Q000209:etiology; D005260:Female; D005340:Fibrinogen / Q000032:analysis / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D007557:Israel; D016013:Likelihood Functions; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D009679:Nuclear Family; D011446:Prospective Studies; D012044:Regression Analysis
D005340:Fibrinogen