GENETIC AND ENVIRONMENTAL SOURCES OF FIBRINOGEN VARIABILITY IN ISRAELI FAMILIES - THE KIBBUTZIM FAMILY STUDY

Genetic and environmental determinants of plasma fibrinogen were inves tigated in a sample of 82 kindreds residing in kibbutz settlements in Israel. The sample included 223 males and 229 females ages 15-37 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 adjus ted fibrinogen levels better than did a single normal distribution. Co mplex segregation analysis was first applied to these sex- and age-adj usted data, Heterogeneous etiologies for individual differences were s uggested. There was evidence for a nontransmitted environmental major factor in addition to polygenic genes that explained the mixture of di stributions, In parallel, a single recessive locus with a major effect that explained the adjusted variation in fibrinogen could not be reje cted. However, when the regression model for sex and age allowed coeff icients to be ousiotype (class)-specific, the recessive genetic model was rejected and the mixed environmental one was not. These results su ggested that particular ousiotypes determined by the major environment al factor are associated with a steeper increase of fibrinogen with ag e. While at the age of 20 years, the major environmental factor contri buted 10% to fibrinogen variability, and 48% was explained by polygeni c loci, at 80 years of age, the major factor explained 64% and only si milar to 20% was explained by polygenic factors.