Borecki I B, Blangero J, Rice T, Pérusse L, Bouchard C, Rao D C
Division of Biostatistics, Washington University School of Medicine, St. Louis, MO 63110, USA.
Am J Hum Genet. 1998 Sep;63(3):831-8. doi: 10.1086/302006.
The genetics of human fatness has been the subject of many recent studies, motivated by the increased morbidity and mortality associated with obesity, as well as the increasing prevalence of overweight and obesity. The body-mass index (BMI) and fat mass (FM), measured by underwater weighing, were assessed for 1,630 individuals from approximately 300 families from phase 1 of the Quebec Family Study. The two phenotypes are highly correlated ( approximately .8) in adults, and previous segregation analysis revealed evidence for a recessive major gene for each trait. In our study, we utilized bivariate segregation analysis to determine the source(s) of phenotypic correlation-namely, a pleiotropic major gene, shared familial factors/polygenes, or shared nontransmitted environmental factors. Analysis was performed by use of the Pedigree Analysis Package, with extensions to the bivariate case. Tests of hypotheses provided evidence for two pleiotropic recessive loci, together accounting for 64% and 47% of the variance in BMI and FM, respectively. Under the model, all sources of phenotypic correlation were significant: 73% of the covariance was attributed to the pleiotropic major loci, 8% to residual familial effects, and 19% to nontransmitted environmental factors. The high degree of genetic identity between the two traits is not surprising, since the BMI often is used as a surrogate for FM; however, simultaneous analysis of both phenotypes enabled the detection of a second major locus, which apparently does not affect extreme overweight (as does the primary major locus) but which affects variation in the "normal" range.
由于肥胖相关的发病率和死亡率上升，以及超重和肥胖的患病率不断增加，人类肥胖遗传学已成为近期许多研究的主题。对来自魁北克家庭研究第一阶段约300个家庭的1630名个体进行了通过水下称重测量的体重指数（BMI）和脂肪量（FM）评估。这两种表型在成年人中高度相关（约为0.8），先前的分离分析揭示了每个性状存在隐性主基因的证据。在我们的研究中，我们利用双变量分离分析来确定表型相关性的来源，即多效性主基因、共享的家族因素/多基因或共享的非传递环境因素。使用系谱分析软件包进行分析，并扩展到双变量情况。假设检验为两个多效性隐性位点提供了证据，这两个位点分别占BMI和FM方差的64%和47%。在该模型下，表型相关性的所有来源都很显著：73%的协方差归因于多效性主位点，8%归因于残余家族效应，19%归因于非传递环境因素。这两个性状之间高度的遗传一致性并不奇怪，因为BMI经常被用作FM的替代指标；然而，对两种表型的同时分析能够检测到第二个主位点，该位点显然不影响极端超重（与主要主位点不同），但影响“正常”范围内的变异。
