Chen Y, Horne S L, Rennie D C, Dosman J A
Centre for Agricultural Medicine, University of Saskatchewan, Saskatoon, Canada.
Genet Epidemiol. 1996;13(1):35-47. doi: 10.1002/(SICI)1098-2272(1996)13:1<35::AID-GEPI4>3.0.CO;2-5.
The Humboldt Family Study was conducted in the town of Humboldt, Saskatchewan, in 1993. Familial correlations and segregation analyses of lung function were carried out in 799 individuals in 214 nuclear families that included 214 fathers, 214 mothers, and 371 children. Forced expiratory volume in 1 second (FEV1) and maximal mid-expiratory flow rate (MMFR) were first regressed on age, height, weight, and their quadratic and cubic terms as well as on smoking status in four groups separately (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 MMFR, father-mother correlations were not significantly different from zero, and mother-offspring, father-offspring, and sibling-sibling correlations showed no statistically significant difference from each other. Based on the "polygenic" models, the estimated intraclass correlation is 0.132 (+/- 0.035) for FEV1 and 0.171 (+/- 0.039) for MMFR, and the narrow-sense heritability is 0.264 for FEV1 and 0.342 for MMFR. Segregation analysis shows that the "mixed" model with both single locus and polygenic components had a better fit for FEV1 than single-locus or polygenic only models. However, the model which included a nontransmitted environmental factor [tau(AA) = tau(AB) = tau(BB) = qA] and polygenic loci had a better fit than the Mendelian model [tau(AA) = 1, tau(AB) = 1/2, tau(BB) = 0] [Akaike's information criterion (AIC) = 2219.47 vs. AIC = 2222.14]. For MMFR, the Mendelian "mixed" model gave a nonsignificant improvement in loge 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 suggests that FEV1 and MMFR are controlled by many loci with no major effects and/or common environmental factors.
洪堡家族研究于1993年在萨斯喀彻温省的洪堡镇开展。对214个核心家庭中的799人进行了肺功能的家族相关性和分离分析，这些家庭包括214名父亲、214名母亲和371名子女。首先分别在四组人群（母亲、父亲、女儿和儿子）中，将一秒用力呼气容积（FEV1）和最大呼气中期流速（MMFR）对年龄、身高、体重及其二次项和三次项以及吸烟状况进行回归分析，保留在0.10水平上显著的项。在四组人群中对残差表型进行标准化处理。使用D类回归模型进行家族相关性和分离分析。对于FEV1和MMFR，父母之间的相关性与零无显著差异，母亲与子女、父亲与子女以及兄弟姐妹之间的相关性彼此之间无统计学显著差异。基于“多基因”模型，FEV1的估计组内相关性为0.132（±0.035），MMFR为0.171（±0.039），FEV1的狭义遗传度为0.264，MMFR为0.342。分离分析表明，具有单基因座和多基因成分的“混合”模型对FEV1的拟合优于仅单基因座或多基因的模型。然而，包含非传递环境因素[tau(AA)=tau(AB)=tau(BB)=qA]和多基因座的模型比孟德尔模型[tau(AA)=1，tau(AB)=1/2，tau(BB)=0][赤池信息准则（AIC）=2219.47对AIC=2222.1）]拟合得更好。对于MMFR，与简单多基因模型相比，孟德尔“混合”模型在对数似然性上的改善不显著。单基因座模型与孟德尔“混合”模型在拟合数据方面无差异。这项研究表明，FEV1和MMFR受许多无主要效应的基因座和/或共同环境因素控制。
