Hanson R L, Elston R C, Pettitt D J, Bennett P H, Knowler W C
Diabetes and Arthritis Epidemiology Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ 85014, USA.
Am J Hum Genet. 1995 Jul;57(1):160-70.
Non-insulin-dependent diabetes mellitus (NIDDM) has a high prevalence in Pima Indians. The disorder is familial, but the extent to which genetic factors are involved in its etiology is largely unknown. Segregation analysis was used to determine whether familial aggregation of NIDDM in this population could reflect the action of a single major gene. The analysis included 2,697 subjects from 653 nuclear families in which both parents and at least one offspring had been examined in the course of a longitudinal epidemiological study. The REGTL program of the SAGE package was used to fit models in which age at onset of NIDDM is transmitted from parent to offspring under the unified model for segregation analysis. Likelihood-ratio tests were used to test hypotheses related to genetic transmission. The hypothesis of no major effect was strongly rejected (P < .01), as was that of no transmission of the major effect (P < .01). Mendelian transmission was not rejected (P = .91). Similar results were obtained when covariates for obesity and birth cohort were added to the models and when a power transformation of age at onset was estimated. A strong effect of birth cohort with earlier age at onset in the later born cohorts was observed (P < .01). The findings are consistent with the hypothesis that a major gene influences the risk for NIDDM in Pima Indians by affecting age at onset. The expression of this gene may depend on environmental factors that have become more prevalent in recent-birth cohorts.
非胰岛素依赖型糖尿病（NIDDM）在皮马印第安人中具有很高的患病率。这种疾病具有家族性，但遗传因素在其病因中所涉及的程度在很大程度上尚不清楚。分离分析被用于确定该人群中NIDDM的家族聚集是否能反映单个主要基因的作用。该分析纳入了来自653个核心家庭的2697名受试者，在一项纵向流行病学研究过程中，对这些家庭的父母双方和至少一个后代都进行了检查。使用SAGE软件包中的REGTL程序来拟合模型，在分离分析的统一模型下，NIDDM发病年龄从父母传递给后代。似然比检验被用于检验与遗传传递相关的假设。无主要效应的假设被强烈拒绝（P <.01），主要效应无传递的假设也被拒绝（P <.01）。孟德尔遗传传递未被拒绝（P =.91）。当将肥胖和出生队列的协变量添加到模型中以及估计发病年龄的幂变换时，也获得了类似的结果。观察到出生队列有很强的效应，较晚出生队列的发病年龄更早（P <.01）。这些发现与以下假设一致，即一个主要基因通过影响发病年龄来影响皮马印第安人患NIDDM的风险。该基因的表达可能取决于在最近出生队列中变得更为普遍的环境因素。
