2型糖尿病的遗传流行病学研究

目的 探讨遗传因素在2型糖尿病发生中的作用及其一般遗传模式。方法 对21个2型糖尿病先证者进行家系调查，应用Falconer同归法估算遗传度，Penrose’s法、Li-Mantel-Gait法及江三多的阈值模型理论估计2型糖尿病分离比、遗传模式等。结果 2型糖尿病先证者一级亲属患病率为7．6％，高于一般人群患病率；2型糖尿病遗传度为46．8％；Penrose’s法计算同胞患病率（s）/人群患病率（q）为3．312，接近1／q^1/2；简单分离分析结果显示，分离率P为0．131，低于0．25；阈值模型理论推算出2型糖尿病一级亲属的理论发病率为8．0％，实际发病率为7．6％。结论 2型糖尿病有明显遗传倾向，但不符合单基因遗传模式，具有多基因遗传特征。     

先天性心脏病的遗传流行病学研究

为探讨先天性心脏病的遗传方式，对３７５例先天性心脏病进行了遗传流行病学研究，结果显示该病一级亲属患病率为６．９％，遗传度６６．１３％±１．１３％；二级亲属患病率为１．７％，遗传度为３８．２５±８．３％，一、二级亲属加权平均遗传度为６５．６５±１．０９％，遗传因素较为重要。在各级亲属患病中，患病率依次为一级亲属（６．９％）、二级亲属（１．７％）、一般群体（０．８６％）。所以该病基本符合多基因遗传方式，遗传在决定先天性心脏病的易患性上起主要作用     

食管癌Y型核心家系宏观遗传流行病学研究

目的 分析遗传因素在肿瘤高发区江苏省扬中市食管癌发病中的作用。方法 采取Y型核心家系设计和遗传流行病学方法，调查分析扬中市409个食管癌及其配偶家系发病情况。结果 病例组一级亲属食管癌的患病率为10．68％，高于对照组亲属的患病率4．69％，RR=2．28。分离比为0．0593，不符合单基因遗传规律，Penrose法分析提示符合多因子遗传模式。阈值模型分析一级亲属遗传度40．13％，女性遗传度44．87％，高于男性的32．78％。结论 食管癌属多基因遗传方式，遗传背景可能是食管癌的主要发病因素之一，遗传易感性因素对女性作用更明显。     

阿尔茨海默病的遗传流行病学研究

目的 探讨遗传因素在阿尔茨海默病发生中的作用及其一般遗传模式.方法 对29个阿尔茨海默病先证者进行家系调查,应用Falconer回归法估算遗传度,应用Penrose's法和江三多的阈值模型理论估计阿尔茨海默病的遗传模式等.结果 阿尔茨海默病先证者Ⅰ级亲属的患病率为5.06％,高于一般人群的患病率(0.912％);阿尔茨海默病的遗传度为53.34％;同胞患病率(s)与人群患病率(q)之比为6.348,接近1/q1/2;阈值模型理论推算出阿尔茨海默病Ⅰ级亲属的理论发病率为5.10％.结论 阿尔茨海默病有明显遗传倾向,但不符合单基因遗传模式,具有多基因遗传特征.     

中国汉族人群系统性红斑狼疮的遗传模式探讨

为探讨系统性红斑狼疮（ＳＬＥ）的遗传模式，应用Ｐｅｎｒｏｓｅ法、最大似然计方法和Ｆａｌｃｏｎ－ｅｒ法对２１５名ＳＬＥ病人及其家系进行了分离分析和遗传度计算，以探讨ＳＬＥ的可能遗传模式。研究结果表明，ＳＬＥ先证者家系一级亲属患病率为０．８５％，高于一般人群患病率（０．０３％）。应用Ｐｅｎｒｏｓｅ法计算，Ｓ／Ｐ接近１／Ｐ；用最大似然估计方法进行简单分离分析，其分离比θ＝０．０２９，经拟合优度χ２检验，χ２＝０．０００１，Ｐ＞０．０５；而经遗传度计算，ｈ２＝５６．７％，Ｐ＜０．０５。遗传模式分析提示，ＳＬＥ不符合单基因遗传模式，而可能是多因子疾病的遗传模式。     

食管癌病因中遗传因素作用的流行病学评价

本文通过对２４９例食管癌病例家族史的调查和病例对照研究，认为食管癌为多基因遗传病，其加权平均遗传度为３２．２０％，病例一，二级血缘亲属患癌的ＳＭＲ值均大于１，且随着血缘关系越接近，其ＳＭＲ值越大，并有统计学显著意义。而对照ＳＭＲ值均显著低于病例相应各级亲属的ＳＭＲ，其值的大小与血缘关系远近无关，说明了遗传因素在食管癌发生中有相当的病因学作用，其一级血缘亲属的归因风险（ＡＲ）可达１２１．３９／１０万。     

2型糖尿病患者遗传性病例对照研究

目的通过对2型糖尿病一级亲属患病率和遗传度的分析，探讨遗传因素在2型糖尿病中的作用。方法采用病例对照方法，选择沈阳市2所医院门诊与住院的2型糖尿病患者203例作为病例组，同期选取社区缝康人群201人作为对照组进行调查。采用χ^2检验进行统计分析，并用Falconer法计算遗传度。结果家族史是2型糖尿病的危险因素（OR=5．89）；病例组一级亲属的2型糖尿病患病率为6。76％，显著高于对照组的1.27％，相对危险度为5．32（95％CI=3.54～7．99）；2型糖尿病一级亲属的遗传度为56．88％。结论遗传因素在2型糖尿病的发生中起重要作用，其一级亲属对糖尿病的遗传易感性较高，是糖尿病预防和控制的重点人群。     

妊娠糖尿病家族遗传模式及遗传度的研究

摘要：目的探讨妊娠糖尿病（GDM）的遗传模式和遗传度。方法选择20个GDM先证的家庭成员,利用流行病学和遗传学方法进行询问调查,包括对家族中有糖尿病（DM）患者的一、二级亲属糖尿病发病年龄、病程发展、治疗方法及并发症等的调查。结果GDM的遗传模式与多基因遗传模式接近,GDM的遗传度为（74．88±10．16）％。结论发生GDM的孕妇本人以及家族成员身上可能存在多个DM相关基因;遗传因素对于GDM的发生有重要作用,但不是唯一的危险因素。     

肝癌遗传模式与危险因素病例-对照研究

目的探讨肝癌的危险因素及遗传模式,为肝癌的预防提供科学依据。方法采用病例-对照研究,以98例肝癌病例和196名健康对照作为研究对象,询问其暴露史;采用Penrose法、简单分离分析和Falconer法对98例原发性肝癌家系资料进行遗传流行病学研究。结果乙肝病史、亲属肿瘤史、食用盐腌食品史、肝硬化病史、饮用地表水与浅井水、饮酒等因素的比值比分别为5.18,8.40,2.16,9.33,2.56,2.61;单基因显性简单分离分析(分离比1/2)χ2=219.44,P<0.01;单基因隐性简单分离分析(分离比1/4)χ2=67.74,P<0.01;应用Penros法计算同胞肝癌发生率,一般人群肝癌发生率(s/q)接近1/q1/2;先证者一级亲属的遗传度为(58.74±5.43)%。结论乙肝病史、亲属肿瘤史、食用盐腌食品史、肝硬化病史、饮用地表水与浅井水、饮酒等是武威市肝癌发病的危险因素;先证者肝癌遗传不符合单基因显性和隐性遗传而是属于多基因遗传,遗传因素对肝癌的发病具有一定的贡献,约占整个危险因素的3/5。     

淮安地区食管癌遗传流行病学研究

[目的]了解遗传因素在淮安地区食管癌发病中的作用及食管癌的遗传模式.[方法]采用以人群为基础的病例对照家系研究,收集97对淮安当地原发性食管癌患者及其对照的家系资料,调查这些家系所有一级亲属的肿瘤发病率;应用多因素非条件Logistic回归估计食管癌家族史的发病风险,Li-Mantel-Gart法计算食管癌的分离比,Penrose法估计遗传模式,Falconer法计算遗传度.[结果]淮安地区食管癌先证者与对照的食管癌家族史差异有统计学意义,先证者家系的一级亲属食管癌患病风险显著高于对照家系,其同胞分离比为0.026(95%CI:0.0003～0.028),Ⅰ级亲属食管癌的遗传度为(24.769±7.038)%.[结论]淮安地区食管癌具有明显的家族聚集性,遗传因素在淮安地区食管癌病因中占一定比重,其遗传模式呈现多基因遗传方式.     

非胰岛素依赖型糖尿病的遗传流行病学研究

目的 探讨非胰岛素依赖型糖尿病一般遗传模式。方法 调查１６０８名在校儿童非胰岛素依赖型糖尿病上、下３代家族史,收集２８０个非胰岛素依赖型糖尿病核心家庭,进行非胰岛素依赖型糖尿病家系资料分析。结果 非胰岛素依赖型糖尿型糖尿病患一级亲属患病率２．３８％,先证父母、同胞、子女患病率分别为２６．００％、２．４４％、１．２４％,高于一般人群患病率;Ｐｅｎｒｏｓｅ法计算同胞患病率／同年龄段患病率为１０．１     

Ⅱ型糖尿病的家庭聚集性研究

目的　通过对Ⅱ型糖尿病家庭聚集性的分析,探讨遗传因素在糖尿病患者一级亲属成员发病中所起的作用及其相对危险度。方法　采用以人群为基础的遗传流行病学病例对照研究方法,对３６３ 例Ⅱ型糖尿病先证者家系及２９１ 例人群对照家系进行了调查。结果　先证者家系一级亲属糖尿病的患病率为３ ．９４ ％ ,对照组一级亲属为１ ．０９ ％ ,相对危险度为３ ．６２ ,各组血缘亲属的相对危险度均在３ ．０ 以上;糖尿病先证者诊断时年龄越轻,其一级亲属的糖尿病患病率和相对危险度越高,其家系内发生多例糖尿病病例的可能性越大。结论　Ⅱ型糖尿病具有明显的家庭聚集倾向,其一级亲属对糖尿病的遗传易感性较高,是糖尿病预防和控制的重点人群。     

Studies on vitiligo. I. Epidemiological profile in Calcutta, India

An epidemiological profile of vitiligo in Calcutta is presented. Prevalence data were gathered from 15,685 individuals drawn from the general population; pedigree data were collected through 293 vitiligo patients. The overall prevalence of vitiligo is about 5 per 1,000 individuals. There are no significant sex or age differences in prevalence rates. About a 4.5-fold increase in prevalence is observed among close biological relatives of affected individuals. There is, however, no clearcut correspondence between relative risks and kinship coefficients. There are no significant differences in the frequencies of various types of vitiligo between probands with and without positive family history. The overall mean and modal ages of onset are about 22 years and 15 years, respectively. The mean ages among males (24.8 years) and females (19.3 years) are significantly different.     

原发性肝癌的遗传流行病学研究

目的　研究原发性肝癌的遗传模式 ,探讨本病的遗传与环境的交互作用。方法　采用Penrose法、简单分离分析和Falconer法对乙型肝炎表面抗原 (HBsAg)阳性队列中的 10 0例原发性肝癌家系资料进行遗传流行病学研究。先证者样本来自同地区 9万名 8年随访队列人群 ,分析遗传模式并将队列中家系样本发病情况分别与队列人群和一般人群的发病情况进行比较 ,计算遗传度。结果　先证者家系一级亲属肝癌发生率为 4 .0 % ,高于一般人群发生率 (0 .4 4 % ) ,也高于队列人群的肝癌发生率 (1.0 3% )。HBsAg阳性在先证者家系中存在聚集 ,且HBsAg阳性与肝癌的发生有强相关(OR =8.4 4 ,95 %CI :3.37～ 2 0 .0 6 ,P <0 .0 0 1) ;应用Penrose法计算 ,同胞肝癌发生率 一般人群肝癌发生率 (s q)接近 1 q1 2 ;简单分离分析提示不符合单因子遗传模式 ;与一般人群遗传度相比 (5 9%±7% ) ,队列人群遗传度h2 =4 2 %± 6 % ,P <0 .0 5。在控制了HBsAg后 ,一般人群遗传度下降为4 7%± 7% ,队列人群遗传度下降为 2 9%± 8%。结论　肝癌不符合单基因遗传模式 ,为一多因子疾病 ,受遗传与环境的综合影响。     

Segregation analysis of cancer in families of glioma patients

A small proportion of brain tumors are attributed to a genetic predisposition; however, the hereditary proportion is undetermined. This study evaluates the degree of familial aggregation of cancer in a large series of brain tumor patients. Our study included 5,088 relatives of 639 probands (3,810 first- and 1,278 second-degree), diagnosed with a glioma between June 1992 and June 1995 at The University of Texas M. D. Anderson Cancer Center, Houston, Texas, with diagnosis under age 65 years, and residents of the United States or Canada. We conducted an in-person or telephone interview with patients and/or their next-of-kin, and obtained family histories for the probands' first-degree (parents, siblings, offspring) and selected second-degree relatives (aunts, uncles, grandparents) using a sequential sampling strategy. Reported cancers were documented by medical records and/or death certificates (if the relative was deceased and medical records were unavailable). We conducted segregation analysis using the Pedigree Analysis Program (PAP). The analyses were divided into two categories: (1) all 639 families, and (2) a subset of families whose gliomas stained positive on p53 immunohistochemistry analysis. We demonstrated that a multifactorial Mendelian model was favored, while a model postulating a purely environmental cause of brain cancer was rejected. This study indicates that familial cancer in relatives of glioma patients are probably a result of multigenic action, and familial clustering of cancer among relatives of glioma patients may involve unknown environmental exposures.     

Segregation analysis of cutaneous melanoma in Queensland

To investigate whether the familial clustering of cutaneous melanoma is consistent with Mendelian inheritance of a major autosomal gene, maximum likelihood segregation analyses were performed in a population-based sample of 1,912 families ascertained through a proband with melanoma diagnosed in Queensland between 1982 and 1990. Analyses were performed with the S.A.G.E. statistical package, using the REGTL program for a binary trait with a variable age of onset. We sought medical confirmation for all family members reported to have had melanoma, and only medically verified cases among relatives were included in the analyses. The hypothesis of codominant Mendelian inheritance gave a significantly better fit to the data than either dominant or recessive Mendelian inheritance, or environmental transmission. Overall, both Mendelian inheritance of a single major gene, and purely environmental transmission were rejected (P < 0.001). In both the single major gene and environmental models, there was strong evidence of familial dependence in melanoma occurrence (P < 0.001). These results are consistent with reported genetic heterogeneity in melanoma inheritance and suggest that other familial factors, such as pigmentation, skin type, and sun exposure habits, may play an important role in the familial clustering of melanoma. Genet. Epidemiol. 15:391–401,1998. © 1998 Wiley-Liss, Inc.     

Effect of cohort differences in smoking prevalence on models of lung cancer susceptibility.

Data on 337 lung cancer families were analyzed to determine if known cohort differences in parental cigarette consumption influence parameters from a segregation analysis. Previous results suggested that, after allowing for an individual's pack-years of tobacco exposure, Mendelian codominant inheritance of an allele that produced an earlier age of onset provided a good fit to the data. In the present study, the data were split into two groups of families: probands age 60 and over (born before WWI) and probands younger than age 60. This partition of the data by age of the proband was done to separate families in which there were parents who were less likely to smoke from those with parents more likely to smoke--predicated on the known increase of smoking prevalence after World War I. For the younger proband families (those with parents more likely to smoke), only Mendelian codominant inheritance adequately fit the data. The hypotheses of no major type, environmental transmission, and Mendelian dominant or recessive inheritance were rejected. In contrast to our earlier findings, the estimate of population susceptibility increased from 28% in the total data to 60% in this subset. In the older proband families (those with parents less likely to smoke), the no major type and environmental hypotheses were rejected; further, none of the Mendelian models could be distinguished. Our results demonstrate that cohort differences, probably in exposure to tobacco, can confound parameters of a segregation analysis, and suggest that the genetic component of lung cancer may be greater than previously estimated. It further suggests that susceptibility to lung cancer occurs as a function of susceptibility to the effects of tobacco smoking.     

遗传因素与原发性高血压

为了探讨遗传因素与原发性高血压的关系，调查了３９个家系父母Ⅱ系Ⅲ级亲属及无血缘关系亲属１５岁以上成人共９３７人。结果表明：有血缘关系高血压患病率明显高于无血缘关系者，分别为３３．３９％和２２．１１％；不同亲属级别高血压患病率Ⅰ级＞Ⅱ级＞Ⅲ级＞一般人群；经Ｌｏｇｉｓｔｉｃ回归分析排除混杂因素后，遗传因素仍独立存在；以遗传因素为背景与其它几个重要危险因素相结合时，也均见到相加模型的增效作用；遗传与共同生活二因素经叉生分析，无论共同生活存在与否，遗传因素恒定存在。     

A family study of vitiligo patterns

The anatomical distribution of vitiligo has been studied in families with evidence of organ-specific autoimmune disease. No examples of similar pattern inheritance were found in first degree relatives in contrast to published reports of similar vitiligo patterns in identical twins. The genetic predisposition to develop vitiligo apparently allows for a diversity of anatomical pattern. A similar mechanism may be responsible for the occurrence of different organ-specific autoimmune diseases in members of the same family.     

Familial aggregation of breast cancer with early onset lung cancer.

Site-specific familial aggregation and evidence supporting Mendelian codominant inheritance have been shown in lung cancer. In characterizing lung cancer families, a number of other cancers have been observed. The current study evaluates whether first-degree relatives of early onset lung cancer cases are at increased risk of breast cancer. Families were identified through population-based lung cancer cases and controls under 40 years of age. Cases were ascertained through the Metropolitan Detroit SEER registry; controls through random-digit dialing. Data were available for 384 female relatives of 118 cases and 465 female relatives of 161 controls. Breast cancer in relatives was evaluated after adjusting for age, race, sex, and smoking status of each family member and the sex and age of the probands. A positive family history of early onset lung cancer increased breast cancer risk among first-degree relatives 5. 1-fold (95% CI, 1.7-15.1). Relatives of cases with adenocarcinoma of the lung were at highest risk (RR = 6.3, 95% CI 2.0-20). Mean age of breast cancer diagnosis among relatives of cases was 52.2 years and not statistically different from relatives of controls. Three case families also reported early ovarian cancers (mean age of diagnosis of 35 years). These findings suggest that shared susceptibility genes may act to increase risk of early onset lung and breast cancer in families.