中国双生子队列研究进展

我国大型人群队列研究方兴未艾,双生子作为一种特殊人群,由于其同时出生、共享母体的宫内环境和早期家庭环境的天然对照优势,可以进行匹配的队列研究,从而很好地控制年龄、性别（同性别双生子）、遗传（同卵双生子）或早期环境（共同抚养的双生子）所带来的混杂,为慢性复杂性疾病病因研究提供不可多得的良好资源。本文将就中国双生子队列的目标、现状、挑战与机遇进行简要介绍,着重呈现双生子不同于一般人群队列的特征。     

上海市双生子出生登记队列建设概况

【目的】建立上海市双生子出生登记队列(STBC),分析遗传因素、共享环境以及非共享环境的相互作用对新生儿出生健康和生长发育的影响。【方法】基于上海市全人群出生队列,筛选2015年1月1日以后出生的户籍双、多胎婴儿家庭进行全面调查,收集双、多胎婴儿的出生健康、生长发育以及家庭环境信息。【结果】截至2021年12月31日,STBC共成功纳入调查的双生子7 195对(14 405例),双生子出生平均身长为47.20 cm,出生平均体重为2 465.30 g,异卵双生子占69.05%,早产儿占57.07%。双生子母亲平均年龄为31.82岁,父亲平均年龄为33.87岁,超过80%的父母文化程度在大专及以上。母亲采用辅助生殖技术的有44.50%,孕期患病的有7.40%,15.90%的母亲孕期存在被动吸烟。调查期间,双胎婴儿的身长平均每月增加2.09 cm,体重平均每月增加0.53 kg。【结论】双生子人群的母亲剖宫产率、新生儿出生早产和低体重等不良结局发生率较高,依托STBC收集双生子人群出生健康以及儿童和青少年期的生长发育信息,为研究儿童慢性非传染性疾病、心理、行为异常等由遗传与环境共同作用的复...     

出生队列效应对体质指数遗传度的影响

目的 探索不同出生队列BMI遗传度的变化情况。方法 基于中国双生子登记系统丽水和青岛两个时点的双生子,按照出生年份分为1958年及以前出生、1959-1961年出生、1962-1970年出生和1971年及以后出生的4个出生队列,在各个时点分别拟合结构方程,计算不同出生队列在不同年龄的遗传度。结果 每个出生队列中,2012年时的体重、BMI高于2001年;出生于1971年及以后的双生子无论体重和BMI均低于其余出生队列。遗传因素能解释BMI的表型变异为54%~76%;出生于1959-1961年的双生子,BMI的遗传度随年龄上升,其余出生队列遗传度较为稳定。结论 BMI受遗传因素影响较大,出生于1959-1961年的双生子,随着年龄增长,遗传因素对BMI的影响增加。     

双生子人群流行病学研究

目的建立以人群为基础的国家双生子登记系统,利用登记系统开展心脑血管疾病及其相关性状的遗传流行病学研究。方法依靠卫生防疫三级保健网络进行双生子募集。结果截至2008年底,中国双生子登记系统共登记双生子8342对,并建立579对双生子队列。在登记系统的基础上,进行一系列具有全部自主知识产权的双生子人群流行病学研究工作,主要包括:卵性鉴定比较研究、双生子长期趋势及影响因素分析、心血管疾病相关中间表型研究、心理学研究以及双生子人群健康状况多维评价研究。结论"双生子人群流行病学研究"充分利用我国双生子资源丰富的特点,探索适合我国国情的双生子登记方法,建立了可用于开展慢性病研究的双生子队列,并创建双生子生物标本库,为复杂疾病病因学研究提供基础和条件。中国双生子登记系统已成为医学和科学研究的一项重要的国际和国内资源。     

生子人群流行病学研究

目的建立以人群为基础的国家双生子登记系统,利用登记系统开展心脑血管疾病及其相关性状的遗传流行病学研究。方法依靠卫生防疫三级保健网络进行双生子募集。结果截至2008年底,中国双生子登记系统共登记双生子8342对,并建立579对双生子队列。在登记系统的基础上,进行一系列具有全部自主知识产权的双生子人群流行病学研究工作,主要包括：卵性鉴定比较研究、双生子长期趋势及影响因素分析、心血管疾病相关中间表型研究、心理学研究以及双生子人群健康状况多维评价研究。结论＂双生子人群流行病学研究＂充分利用我国双生子资源丰富的特点,探索适合我国国情的双生子登记方法,建立了可用于开展慢性病研究的双生子队列,并创建双生子生物标本库,为复杂疾病病因学研究提供基础和条件。中国双生子登记系统已成为医学和科学研究的一项重要的国际和国内资源。     

成年期慢性非传染性疾病早期起源的研究进展基于赫尔辛基出生队列研究

赫尔辛基出生队列研究历经数十年的长期随访,获得了一系列生命早期生长发育与成年期慢性非传染性疾病相关的研究成果,为揭示成年期慢性非传染性疾病发生发展的起因和早期预防提供了科学依据。现对该出生队列关于成年期慢性非传染性疾病早期起源的主要研究成果进行综述,为我国开展大型出生队列研究提供一定的经验借鉴。     

中国国家出生队列孤独症谱系障碍亚队列建设概况

孤独症谱系障碍作为儿童神经发育障碍的代表性疾病,发病率呈现不断上升的趋势,给家庭和社会带来巨大压力和经济负担,探讨其病因及发病机制意义重大。本研究依托中国国家出生队列开展孤独症谱系障碍亚队列建设,并利用该出生队列采用的辅助生殖和自然妊娠同期纳入并随访的平行设计,评价辅助生殖技术对子代神经行为发育的影响,并结合队列采集的多种母体孕期和子代生命早期临床及行为相关信息,综合探究孤独症谱系障碍的发病危险因素。本文将从研究目标、内容、初步进展、优势与不足及进一步展望对该亚队列进行简要介绍,重点展现本研究的总体设计和现阶段进展。     

出生队列技术规范第1部分:现场调查(T/CPMA 015.1-2020)

出生队列研究的现场调查围绕研究人群的环境、遗传、生活行为习惯等因素和生殖健康相关结局开展信息和生物样本采集,是出生队列建设不可或缺的重要基础。本文件就出生队列研究现场调查中的机构设置、现场准备、队列编码体系、研究对象招募及质量控制等主要工作制定规范。     

双生子方法在糖尿病析因研究中的应用进展

糖尿病是一种由遗传和环境因素共同作用导致的复杂疾病,严重影响人群健康水平和生存质量,双生子方法作为特殊的研究工具,可以估计基因和环境对糖尿病相关性状的相对作用。与一般研究对象相比,双生子拥有自然对照,结合遗传统计学和分子生物学技术进行方法学的拓展,有助于解析疾病危险因素,明确暴露与结局的真实关联。本文对国内外近十年来双生子方法在糖尿病析因研究中的应用进展进行了综述,总结了经典双生子模型、对内对照研究、全基因组和表观遗传流行病学研究等方法的优势和局限性。     

上海市3089对双生子身高、体重的差异特点

[目的]比较不同卵型、年龄组双生子间体重、身高和体质量指数(BMI)的差异,为研究遗传与环境对生长发育的影响提供基础数据。[方法]通过2013年在上海市范围内实施的中国环境流行病学人群队列研究双生子队列上海项目,入户调查收集双生子体重、身高、BMI等指标,通过方差分析计算上述3项指标的差值及其差比率在不同卵型、不同年龄段双生子间的差异。[结果]最终纳入本研究的双生子共3 089对,其中同卵1 772对,异卵1 317对。除60岁及以上男性双生子外,各年龄组同卵双生子间体重、身高和BMI差的差异均小于异卵双生子(P0.05)。未发现20岁及以下双生子间3项指标差比率随年龄段不同而不同(P0.05)。[结论]相较于环境因素,遗传因素在体重、身高方面起着更重要的作用。     

基于基因与环境交互作用的儿童肥胖病因研究进展

儿童肥胖是全球性的公共健康问题,不仅危害儿童自身健康,还是成年期慢性病发病的重要诱因。近年来,随着精准医学研究的深入开展,越来越多的研究证据指明环境、行为因素,如早期宫内环境、儿童饮食、体力活动等,与儿童自身基因风险对肥胖的发病具有显著的交互作用,可以促进或抑制儿童肥胖的发生发展。本文对该领域现有研究进行综述,总结基因风险和环境暴露因素对儿童肥胖发病的交互作用及潜在机制,为不同遗传背景儿童的肥胖精准防控提供参考依据。     

Influence of Genetics on Disease Susceptibility and Progression

For many chronic diseases, the influence of genetics is complex and phenotypes do not conform to simple Mendelian patterns of inheritance. Discussed here are two types of genetic influences on healthy aging. The first involves variation in the gene sequence itself and how this may influence disease susceptibility, progression, and severity, interacting with other recognized risk factors. The second involves epigenetic regulatory mechanisms that may potentially provide insight into how environmental influences affect the expressed genome, thus improving our understanding of the genetic mechanisms underlying multifactorial diseases. The interleukin-1 family of cytokines can be used to illustrate how genetic sequence variation may affect such diseases. This cytokine family plays a key role in mediating inflammation, which is now understood to be a central component of a growing number of chronic diseases. Recent work has revealed many sequence variations in the regulatory DNA of genes encoding important members of the interleukin-1 family, and these variations are associated with differential effects on the inflammatory response. The interactions of environmental factors with both DNA sequence variations and epigenetic modifications are likely to determine the phenotypes of multifactorial diseases of aging as well as the phenotype of healthy aging.     

北方农村地区居民常见慢性非传染性疾病的家系队列研究进展

家系队列研究是一种特殊的队列研究方法,以家系为单位收集研究对象的生物样本和环境暴露信息,并进行随访,为探索复杂性疾病病因研究中遗传、环境、基因-基因和基因-环境交互作用提供重要资源。本文将对“北方农村地区居民常见慢性非传染性疾病的家系队列研究”的目标、方法、初步结果、机遇与挑战进行简单介绍。     

Why are children in the same family so different from one another?

One of the most important findings that has emerged from human behavioral genetics involves the environment rather than heredity, providing the best available evidence for the importance of environmental influences on personality, psychopathology, and cognition. The research also converges on the remarkable conclusion that these environmental influences make two children in the same family as different from one another as are pairs of children selected randomly from the population. The theme of the target article is that environmental differences between children in the same family (called "nonshared environment") represent the major source of environmental variance for personality, psychopathology, and cognitive abilities. One example of the evidence that supports this conclusion involves correlations for pairs of adopted children reared in the same family from early in life. Because these children share family environment but not heredity, their correlation directly estimates the importance of shared family environment. For most psychological characteristics, correlations for adoptive "siblings" hover near zero, which implies that the relevant environmental influences are not shared by children in the same family. Although it has been thought that cognitive abilities represent an exception to this rule, recent data suggest that environmental variance that affects IQ is also of the nonshared variety after adolescence. The article has three goals: (1) To describe quantitative genetic methods and research that lead to the conclusion that nonshared environment is responsible for most environmental variation relevant to psychological development, (2) to discuss specific nonshared environmental influences that have been studied to date, and (3) to consider relationships between nonshared environmental influences and behavioral differences between children in the same family. The reason for presenting this article in BBS is to draw attention to the far-reaching implications of finding that psychologically relevant environmental influences make children in a family different from, not similar to, one another.     

出生缺陷危险因素及诊断研究进展

出生缺陷正在成为婴儿死亡的主要原因,是目前全世界关注的一个重大公共卫生问题.出生缺陷可由遗传因素如染色体畸变、基因突变引起,也可由环境致畸因素或两者共同作用所致.我国出生缺陷发生率呈上升趋势.这些缺陷类型如果通过早期诊断、早期干预,其中至少70%可以避免.出生缺陷干预是一个系统工程,需要全社会参与.产前超声筛查和母体血清生化指标检测是胎儿出生缺陷干预的有效手段,是出生缺陷干预二级预防中的重要组成部分.     

Estimation of genetic and environmental factors for melanoma onset using population-based family data

Estimation of genetic and environmental contributions to cancers falls in the framework of generalized linear mixed modelling with several random effect components. Computational challenges remain, however, in dealing with binary or survival phenotypes. In this paper, we consider the analysis of melanoma onset in a population of 2.6 million nuclear families in Sweden, for which none of the current survival-based methodologies is feasible. We treat the disease outcome as a binary phenotype, so that the standard proportional hazard model leads to a generalized linear model with the complementary-log link function. For rare diseases this link is very close to the probit link, and thus allows the use of marginal likelihood for the estimation of the variance components. We correct for the survival length bias by censoring the parent generation within each family at the time they attain the same cumulative hazard as the child generation, thus improving the validity of the estimates. Our finding that childhood shared environment in addition to genetic factors had a considerable effect on the development of melanoma is consistent with epidemiological studies.     

The role of early life environmental risk factors in Parkinson disease: what is the evidence?

Parkinson disease (PD) is of unknown but presumably multifactorial etiology. Neuropathologic studies and animal models show that exposure to environmental neurotoxicants can determine progressive damage in the substantia nigra many years before the onset of clinical parkinsonism. Therefore, PD, like other neurologic diseases related to aging, may be determined by exposures present in the environment early during the life span or even during pregnancy. Recent epidemiologic studies have focused on the possible role of environmental risk factors present during adult life or aging. Smoking and coffee drinking have consistently been identified to have protective associations, whereas roles of other risk factors such as pesticide and infections have been reported in some studies but not replicated in others. Both genetic inheritance and sharing of common environment in the same family explain the increased risk of PD of relatives of PD cases compared with relatives of controls in familial aggregation studies. Much evidence indicates that risk factors that have a long latency or a slow effect could be important for late-onset PD. Further epidemiologic studies are warranted in this area.     

利用人口计划生育服务网络开展出生缺陷预防

提高出生人口素质的重要内容之一是预防出生缺陷。出生缺陷发生的病因比较复杂,既有遗传因素也有环境因素,应从社会、医学、环境、行为等多方面开展出生缺陷预防工作。对目前出生缺陷流行状况、中国出生缺陷干预面临的挑战,以及利用人口计划生育网络开展出生缺陷预防的成功实践做文献综述。     

Co-localization of differentially expressed genes and shared susceptibility loci in human autoimmunity

Autoimmune diseases arise from complex interactions between environmental and genetic factors. Genetic linkage scans show that different autoimmune diseases share overlapping susceptibility loci. Lymphocytes from individuals with different autoimmune diseases, as well as unaffected first-degree relatives, also share a common gene expression profile. We sought to determine if genes within this autoimmune expression profile were nonrandomly distributed in the genome and if their distribution overlapped with shared disease susceptibility loci. We found that differentially expressed genes were distributed in a nonrandom fashion in chromosomal domains within the genome. Furthermore, positions of these domains were not statistically different from a number of shared autoimmune disease susceptibility loci. To our knowledge, this is the first study showing concordance between gene expression and genetic linkage results in common complex multifactorial human diseases.