Concordance odds ratios and approximate rate ratios in longitudinal twin studies

Odds ratios derived from probandwise concordance rates are usually interpreted as increased risks in twins. Though the odds ratios in case–control studies have been shown to reflect rate ratios, few studies focused on such relationships in twin studies. The authors derived an approximate formula for the ratios of person-time incidence rates after the random assignment of twins into index twins and co-twins, i.e., incidence rate ratios. The resulting rate ratio was estimated as the product of the concordance odds ratio and a term that reflect the follow-up duration and the average time to occurrence of disease. Odds ratios coincide with rate ratios when the average time to occurrence of disease is half the duration of follow-up, although in studies spanning several decades these two measures might be different. The authors illustrated that when the incidence rate is not constant over the follow-up period as in longitudinal twin studies, the conventional odds ratio should not be used as an estimator of rate ratio.     

双胎新生儿出生体重不一致对其之一并发症发生风险影响

目的 探讨双胎新生儿出生体重差值(ΔBW)预测双胎新生儿之一发生并发症的临床意义。方法 选择2018年1月至2019年12月,在南京大学医学院附属鼓楼医院分娩的752对(1 504例)活产双胎新生儿,及其母亲为研究对象。根据双胎新生儿是否发生并发症(双胎新生儿之一或双胎新生儿均发生并发症),将其分别纳入研究组(n=178)和对照组(n=574);再根据研究组双胎新生儿是否被转入新生儿重症监护病房(NICU),进一步分为NICU亚组(n=153)和非NICU亚组(n=25)。影响双胎新生儿之一发生并发症因素进行单因素分析和多因素非条件logistics回归分析,并绘制预测双胎新生儿之一总体并发症的受试者工作特征(ROC)曲线。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》要求,并经南京大学医学院附属鼓楼医院伦理委员会审核批准(批准文号：2020-264)。结果 (1)752对双胎中,178对双胎新生儿之一发生并发症,发生率为23.7%(178/752)。(2)研究组双胎的剖宫产术分娩率、辅助生殖率、出生胎龄与体重及Apgar评分均低于对照组,而研究组产妇妊娠期高血压疾病...     

Upward bias in odds ratio estimates from genome-wide association studies

Genome-wide association studies are carried out to identify unknown genes for a complex trait. Polymorphisms showing the most statistically significant associations are reported and followed up in subsequent confirmatory studies. In addition to the test of association, the statistical analysis provides point estimates of the relationship between the genotype and phenotype at each polymorphism, typically an odds ratio in case-control association studies. The statistical significance of the test and the estimator of the odds ratio are completely correlated. Selecting the most extreme statistics is equivalent to selecting the most extreme odds ratios. The value of the estimator, given the value of the statistical significance depends on the standard error of the estimator and the power of the study. This report shows that when power is low, estimates of the odds ratio from a genome-wide association study, or any large-scale association study, will be upwardly biased. Genome-wide association studies are often underpowered given the low alpha levels required to declare statistical significance and the small individual genetic effects known to characterize complex traits. Factors such as low allele frequency, inadequate sample size and weak genetic effects contribute to large standard errors in the odds ratio estimates, low power and upwardly biased odds ratios. Studies that have high power to detect an association with the true odds ratio will have little or no bias, regardless of the statistical significance threshold. The results have implications for the interpretation of genome-wide association analysis and the planning of subsequent confirmatory stages.     

Stepping towards causation in studies of neighborhood and environmental effects: How twin research can overcome problems of selection and reverse causation

No causal evidence is available to translate associations between neighborhood characteristics and health outcomes into beneficial changes to built environments. Observed associations may be causal or result from uncontrolled confounds related to family upbringing. Twin designs can help neighborhood effects studies overcome selection and reverse causation problems in specifying causal mechanisms. Beyond quantifying genetic effects (i.e., heritability coefficients), we provide examples of innovative measures and analytic methods that use twins as quasi-experimental controls for confounding by environmental effects. We conclude that collaboration among investigators from multiple fields can move the field forward by designing studies that step toward causation.     

Comparison of methods for analyzing binary data arising from two-sample twin studies

The study of twins is widely used for research into genetic and environmental influences on human outcome measurements. For the study design in which independent samples of monozygotic and dizygotic twins are compared with respect to their similarity on a binary trait, several statistical methods have been proposed. Using a Monte Carlo simulation, we compare the five following procedures: 1) goodness-of-fit method based on the common correlation model, 2) normal approximation of the maximum likelihood estimators of the common correlation coefficients, 3) Ramakrishnan et al. [(1992) Genet Epidemiol 9:273–282] method of odds ratio comparison, 4) generalized estimating equations method of odds ratio estimation, and 5) tetrachoric correlation method. The results show that the goodness-of-fit approach has similar or better performance in both type-one error rates and power than the other methods in all parameter settings. Its advantage with respect to type-one error rates is particularly clear under conditions of small sample sizes, extreme prevalences, or high values of the intraclass correlation coefficients. Therefore, the goodness-of-fit method is recommended for the two-sample twin study design. Genet. Epidemiol. 14:349–363,1997. © 1997 Wiley-Liss, Inc.     

Further results on covariate measurement errors in cohort studies with time to response data

The impact of covariate measurement errors on the estimation of relative risk regression parameters is discussed. First the dependence of the induced relative risk process on the cumulative baseline failure rate function is noted. Next induced relative risk models under some specific failure time and measurement error models are described, including the much simplified models that are appropriate under a 'rare disease' assumption. The presentation then turns to the joint estimation of relative risk parameters of primary interest along with measurement error parameters. A partial likelihood product is proposed for such estimation and asymptotic properties are indicated. Guidance is also presented as to the appropriate size of a 'validation' sample relative to the full cohort size. Finally some more general considerations are presented as to the usefulness and interpretation of deattenuated regression coefficients.     

Improved correction for population stratification in genome-wide association studies by identifying hidden population structures

Hidden population substructure can cause population stratification and lead to false-positive findings in population-based genome-wide association (GWA) studies. Given a large panel of markers scanned in a GWA study, it becomes increasingly feasible to uncover the hidden population substructure within the study sample based on measured genotypes across the genome. Recognizing that population substructure can be displayed as clustered and/or continuous patterns of genetic variation, we propose a method that aims at the detection and correction of the confounding effect resulting from both patterns of population substructure. The proposed method is an extension of the EIGENSTRAT method (Price et al. [2006] Nat Genet 38:904-909). This approach is computationally feasible and easily applied to large-scale GWA studies. We show through simulation studies that, compared with the EIGENSTRAT method, the new method requires a smaller number of markers and yields a more appropriate correction for population stratification.     

B-Lynch改良缝合法预防双胎妊娠剖宫产术后出血

目的探讨B-Lynch改良缝合法预防双胎妊娠剖宫产术后出血的临床效果。方法对双胎妊娠手术152例采用前瞻性观察方法,随机分为观察组（B-Lynch改良缝合组）76例和对照组（常规处理组）76例,观察两组术中出血量、术后24h出血量。结果观察组术中、术后24h出血量明显低于对照组,组间差异有统计学意义（P〈0.05）;观察组产后出血、产褥病发生率明显低于对照组,差异有统计学意义（P〈0.05）。结论 B-Lynch改良缝合法预防双胎妊娠剖宫产术后出血效果明显,值得临床推广。     

腰椎和髋部骨密度的相关性及对骨质疏松诊断的差异性分析

随着全球人口老龄化加剧,骨质疏松症(OP)发病率逐年增加并已成为世界公共卫生问题.骨密度(BMD)测定对OP诊断、防治、骨折风险评估有重要意义,不同种族、性别、年龄、骨骼部位其BMD变化规律及OP检出率不同.本研究检测成都市城区中老年健康人群腰椎与髋部BMD,观察不同部位检测相关性及对OP诊断的影响.     

病例对照研究中logistic回归参数估计的应用条件研究

目的通过计算机模拟抽样,对病例对照研究资料logistic回归模型参数极大似然估计方法的应用条件进行探讨,为正确应用该法提供理论基础和应用指导.方法利用SAS函数抽取四格表资料,应用LogXact软件计算MLE及精确推断结果,对其进行比较.结果当暴露比低于0.1,尤其是OR比较大的情况下,MLE法必须满足大样本条件;随着暴露比的增加,MLE法对样本含量的要求可以放宽,暴露比为0.2,每组样本例数可为15例.结论MLE法估计logistic模型参数对样本含量的要求可以有条件的放宽;精确推断是MLE法的补充.     

logistic回归参数遗传算法估计的可行性研究

目的 考察遗传算法作为logistic回归模型参数估计方法的效能,并与极大似然估计法比较.方法 通过数据模拟建立三种模型,分别用遗传算法和极大似然法作参数估计,考察建立模型的分类效能.结果 一般情况下,极大似然估计法的分类效能稍高于遗传算法.在样本量较小或自变量关系复杂的情况下,极大似然估计法和遗传算法的泛化误差增加.极大似然估计法的泛化误差主要源于在验证集中分类效能下降,而遗传算法的泛化误差主要源于训练集中的过拟合.当样本量小且自变量关系复杂的情况下,极大似然估计法出现迭代不收敛,参数失拟合,遗传算法无此现象.结论 遗传算法适用于自变量多而样本量相对小时logistic回归模型参数估计.     

非线性因子分析模型参数估计研究

目的研究非线性因子分析模型的参数估计方法.方法利用MCECM算法对模型参数进行极大似然估计,利用Louis公式计算标准误.结果统计模拟结果显示估计值与真实值比较吻合,误差较小.结论基于MCECM算法的极大似然估计方法可用于估计非线性因子分析模型的参数.     

中国11省市35～64岁人群应用不同代谢综合征诊断标准的比较

目的比较美国国家胆固醇教育计划成人治疗方案第三次报告(NCEP-ATPⅢ)、国际糖尿病联盟(IDF)和中华医学会糖尿病学分会(CDS)建议的代谢综合征(MS)诊断标准在中国35～64岁人群中应用的差异。方法1992年对中国11省市35～64岁人群共29 564人进行了心血管病危险因素基线调查,1996—1999年又入选了35～64岁男女两性共3129人,分别应用三种标准计算该人群MS的患病率,分析不同标准时MS异常组分及危险因素聚集的检出情况,比较三种标准在中国人群中应用的一致性和差异。结果(1)应用ATPⅢ、IDF和CDS标准计算中国人群MS的年龄标化患病率分别为18.7%、14.6%和9.0%。(2)ATPⅢ诊断MS中有77.8%的人有中心性肥胖,22.2%无中心性肥胖;IDF诊断为非MS者中还有4.6%的人有3个及以上危险因素聚集;CDS诊断为非MS者中还有11.2%的人有3个及以上危险因素聚集。(3)ATPⅢ和IDF诊断标准在中国人群中应用的一致性较好,男女两性的Kappa值分别为0.795和0.899;CDS诊断标准与另两种诊断标准的一致性不高。(4)男性腰围切点为85 cm,女性腰围切点为80 cm时,预测危险因素聚集的ROC曲线距离分别为0.40和0.34,其在所选择的切点中ROC曲线距离相对最短。结论在三种MS诊断标准中,ATPⅢ诊断中国人群MS的患病率及检出危险因素聚集的比例最高;适宜中国人群的最佳腰围切点为男性85 cm、女性80 cm。     

Meta‐analysis of ratios of sample variances

When conducting a meta‐analysis of standardized mean differences (SMDs), it is common to use Cohen's d, or its variants, that require equal variances in the two arms of each study. While interpretation of these SMDs is simple, this alone should not be used as a justification for assuming equal variances. Until now, researchers have either used an F‐test for each individual study or perhaps even conveniently ignored such tools altogether. In this paper, we propose a meta‐analysis of ratios of sample variances to assess whether the equality of variances assumptions is justified prior to a meta‐analysis of SMDs. Quantile–quantile plots, an omnibus test for equal variances or an overall meta‐estimate of the ratio of variances can all be used to formally justify the use of less common methods when evidence of unequal variances is found. The methods in this paper are simple to implement and the validity of the approaches are reinforced by simulation studies and an application to a real data set. Copyright © 2016 John Wiley & Sons, Ltd.     

A comparison of tests of homogeneity of odds ratios in K 2 x 2 tables

We conducted a simulation study to determine the performance of nine procedures for testing the homogeneity of odds ratios in K 2 x 2 contingency tables. We recommend Tarone's approximate score test, based on the Mantel-Haenszel estimator of the common odds ratio, for use in practice. We also recommend a non-iterative statistic developed by Gart and based on the modified Woolf estimator of the common odds ratio for very large samples in balanced or mildly unbalanced designs. We base our recommendation of a statistic on its performance in terms of size and power in comparison with the other statistics considered.     

利用结构方程模型计算双生子一侧优势功能特征的遗传度

目的 分析遗传和环境因素分别对3项一侧优势功能特征的影响.方法 对在青岛市和丽水市两地募集的511对双生子进行一侧优势功能(利手、扣手、交叉臂方式)的判定,计算3项左型性状的一致率、卵别比值比、四项相关系数,并用openMx软件进行遗传模型的拟合.结果 左利手的最佳拟合为AE模型,遗传度为45.5％,左型扣手和左型交叉臂的最佳模型为DE模型,显性遗传效应分别是13.5％和6.1％.年龄和性别对遗传效应的影响无统计学意义.结论 左利手的遗传度为45.5％,扣手和交叉臂的遗传表现为显性遗传,但主要受环境影响.     

双生子的血清脂质和脂蛋白遗传度及影响因素分析

目的　分析儿童、青少年的血脂指标遗传度及影响因素。方法　选择 5～ 19岁双生子2 36对 ,平均年龄 (11 2± 3 4 )岁 ,其中同卵双生子 14 3对 ,异卵双生子 93对。在DNA卵性鉴定基础上 ,以组内相关系数法及Falconer公式计算调整年龄性别前后的遗传度 ,偏态数据进行对数转换 ;校正年龄性别 ,分析相关体格、生化指标对血脂的影响。结果　同卵与异卵双生子间甘油三酯对内方差及相关系数的差异均无显著性 ;总胆固醇、高密度脂蛋白胆固醇 (HDL C)、低密度脂蛋白胆固醇 (LDL C)和脂蛋白 (a)对内方差及相关系数的差异有显著性 ,遗传度估计值分别为 0 5 6、0 5 5、0 4 9和 0 5 8,调整年龄性别后各指标估计遗传度分别为 0 6 3、0 6 3、0 5 5和 0 6 4。总胆固醇、HDL C、LDL C和脂蛋白(a)与年龄呈负相关 ;女孩的总胆固醇、HDL C、LDL C稍高于男孩。校正年龄性别后除脂蛋白 (a)外各血脂指标多数与体重指数、体脂率及培利迪西指数相关 ,与血压、血糖和血钙等也有相关性。结论　总胆固醇、HDL C、LDL C和脂蛋白 (a)受遗传因素影响较大 ,而甘油三酯主要受环境因素影响。儿童的血脂水平受年龄和性别的影响 ,与反映体脂和机体营养发育的指标相关。     

Use of death certificates in epidemiological studies, including occupational hazards: discordance with clinical and autopsy findings.

There has long been evidence of frequent inaccuracy of death certificates, with significant discordance between such designations and clinical and autopsy data. This exists for occupational diseases as well. The use of statistical rates based on death certificates has been seriously questioned despite their utility for total mortality. Programs to supplement death certificate data, particularly in occupational disease studies, may be helpful, and are reviewed.     

The interpretation of exposure effect estimates in chronic air pollution studies

In this article we consider the interpretation of regression parameters used to represent 'chronic' or 'long-term' air pollution exposure effects. Although scientific interest typically lies in understanding such effects at the level of the individual, studies have generally employed a semi-ecological design; outcomes and confounder information are collected on individuals while exposure is only available at the aggregate-or group-level. A precise interpretation of results from a semi-ecological design must take into account the aggregated nature, both spatial and temporal, of the exposure measure. The most common analysis approach for assessing chronic exposure effects has been within the Cox proportional hazards model framework; specific analyses are tailored to accommodate the shortcomings of the available exposure information. We revisit the underlying assumptions of the Cox model and discuss the implications of two common aspects of chronic effects studies: time-dependent exposures and time-varying effects. Focusing on the consequences of temporal aggregation of exposure, we show that an estimate obtained from a time-aggregated semi-ecological design can correspond to very different underlying time-varying exposure and risk scenarios. Further, distinguishing which of these is correct is not possible from the semi-ecological data alone. Our goal is to highlight some statistical issues faced by existing studies of chronic air pollution effects, and aid in the development and planning of future studies.