Y. Chen et al., SEGREGATION ANALYSIS OF 2 LUNG-FUNCTION INDEXES IN A RANDOM SAMPLE OFYOUNG FAMILIES - THE HUMBOLDT FAMILY STUDY, Genetic epidemiology, 13(1), 1996, pp. 35-47
The Humboldt Family Study was conducted in the town of Humboldt, Saska
tchewan, in 1993. Familial correlations and segregation analyses of lu
ng function were carried out in 799 individuals in 214 nuclear familie
s that included 214 fathers, 214 mothers, and 371 children. Forced exp
iratory volume in 1 second (FEV1) and maximal mid-expiratory flow rate
(MMFR) were first regressed on age, height, weight, and their quadrat
ic and cubic terms as well as on smoking status in four groups separat
ely (mothers, fathers, daughters, and sons), with terms significant at
the 0.10 level being retained. Residual phenotypes were standardized
within the four groups. Class D regressive models were used to perform
familial correlations and segregation analyses. For both FEV1 and MMF
R, father-mother correlations were not significantly different from ze
ro, and mother-offspring, father-offspring, and sibling-sibling correl
ations showed no statistically significant difference from each other.
Based on the ''polygenic'' models, the estimated intraclass correlati
on is 0.132 (+/- 0.035) for FEV1 and 0.171 (+/- 0.039) for MMFR, and t
he narrow-sense heritability is 0.264 for FEV, and 0.342 for MMFR. Seg
regation analysis shows that the ''mixed'' model with both single locu
s and polygenic components had a better fit for FEV1 than single-locus
or polygenic-only models. However, the model which included a nontran
smitted environmental factor [tau(AA) = tau(AB) = tau(BB) = qA] and po
lygenic loci had a better fit than the Mendelian model [tau(AA) = 1, t
au(AB) = 1/2, tau(BB) = 0] [Akaike's information criterion (AIC) = 221
9.47 vs. AIC = 2222.14]. For MMFR, the Mendelian ''mixed'' model gave
a nonsignificant improvement in log, likelihood compared to the simple
polygenic model. Comparison of the single-locus model and Mendelian '
'mixed'' model shows no difference in fitting the data. This study sug
gests that FEV1 and MMFR are controlled by many loci with no major eff
ects and/or common environmental factors. (C) 1996 Wiley-Liss, Inc.