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遗传风险评分构建：投影汇总统计与灵活收缩的稳健贝叶斯方法AI 解读

Polygenic risk scores (PRS) developed from genome-wide association studies (GWAS) can be used for risk stratification by quantifying the genetic contribution to disease, and many clinical applications have been proposed. Bayesian methods are popular for building PRS because of their natural ability to regularize models and incorporate external information. In this article, we present new theoretical results, methods, and extensive numerical studies to advance Bayesian…

融合 GWAS 汇总统计与外部信息的多基因风险惩罚回归AI 解读

Large-scale genome-wide association studies (GWAS) provide opportunities for developing genetic risk prediction models that have the potential to improve disease prevention, intervention or treatment. The key step is to develop polygenic risk score (PRS) models with high predictive performance for a given disease, which typically requires a large training dataset for selecting truly associated single nucleotide polymorphisms (SNPs) and estimating effect sizes accurately.…

协变量信息不一致研究的多元回归广义元分析AI 解读

Summary Meta-analysis is widely popular for synthesizing information on common parameters of interest across multiple studies because of its logistical convenience and statistical efficiency. We develop a generalized meta-analysis approach to combining information on multivariate regression parameters across multiple studies that have varying levels of covariate information. Using algebraic relationships among regression parameters in different dimensions, we specify a set…

聚合关联检验后的选择后估计与检验AI 解读

Summary The practice of pooling several individual test statistics to form aggregate tests is common in many statistical applications where individual tests may be underpowered. Although selection by aggregate tests can serve to increase power, the selection process invalidates inference based on the individual test statistics, making it difficult to identify those that drive the signal in follow-up inference. Here, we develop a general approach for valid inference following…

大规模基因组数据中聚合层检验后的选择后推断AI 解读

In many genomic applications, hypotheses tests are performed for powerful identification of signals by aggregating test-statistics across units within naturally defined classes. Following class-level testing, it is naturally of interest to identify the lower level units which contain true signals. Testing the individual units within a class without taking into account the fact that the class was selected using an aggregate-level test-statistic, will produce biased inference.…

病例对照研究中复杂多基因与环境交互作用的半参数分析AI 解读

Many methods have recently been proposed for efficient analysis of case-control studies of gene-environment interactions using a retrospective likelihood framework that exploits the natural assumption of gene-environment independence in the underlying population. However, for polygenic modelling of gene-environment interactions, which is a topic of increasing scientific interest, applications of retrospective methods have been limited due to a requirement in the literature…

利用外部大数据汇总信息校准模型的约束最大似然估计AI 解读

Information from various public and private data sources of extremely large sample sizes are now increasingly available for research purposes. Statistical methods are needed for utilizing information from such big data sources while analyzing data from individual studies that may collect more detailed information required for addressing specific hypotheses of interest. In this article, we consider the problem of building regression models based on individual-level data from…

病例对照数据二次分析中同方差回归的稳健估计AI 解读

Summary Primary analysis of case–control studies focuses on the relationship between disease D and a set of covariates of interest (Y, X). A secondary application of the case–control study, which is often invoked in modern genetic epidemiologic association studies, is to investigate the interrelationship between the covariates themselves. The task is complicated owing to the case–control sampling, where the regression of Y on X is different from what it is in the population.…

单调性约束下的基因—环境与基因—基因交互检验AI 解读

Recent genome-wide association studies (GWASs) designed to detect the main effects of genetic markers have had considerable success with many findings validated by replication studies. However, relatively few findings of gene–gene or gene–environment interactions have been successfully reproduced. Besides the main issues associated with insufficient sample size in current studies, a complication is that interactions that rank high based on p-values often correspond to…

部分问卷设计与非单调缺失下半参数回归模型的推断AI 解读

In epidemiologic studies, partial questionnaire design (PQD) can reduce cost, time, and other practical burdens associated with lengthy questionnaires by assigning different subsets of the questionnaire to different, but overlapping, subsets of the study participants. In this article, we describe methods for semiparametric inference for regression model under PQD and other study settings that can generate nonmonotone missing data in covariates. In particular, motivated from…

单倍型病例对照研究中兼顾稳健性与效率的收缩估计AI 解读

Case-control association studies often aim to investigate the role of genes and gene-environment interactions in terms of the underlying haplotypes (i.e., the combinations of alleles at multiple genetic loci along chromosomal regions). The goal of this article is to develop robust but efficient approaches to the estimation of disease odds-ratio parameters associated with haplotypes and haplotype-environment interactions. We consider "shrinkage" estimation techniques that can…

含交互作用的半参数模型检验及基因—环境交互应用AI 解读

Summary Motivated from the problem of testing for genetic effects on complex traits in the presence of gene–environment interaction, we develop score tests in general semiparametric regression problems that involves Tukey style 1 degree-of-freedom form of interaction between parametrically and non-parametrically modelled covariates. We find that the score test in this type of model, as recently developed by Chatterjee and co-workers in the fully parametric setting, is biased…

乳腺密度数据缺失时病例对照与队列设计中的乳腺癌相对风险估计AI 解读

We analyzed data from the Breast Cancer Detection Demonstration Project (BCDDP) to obtain multivariate relative hazard models for breast cancer that included mammographic density (MD) in addition to standard risk factors. Data from the BCDDP were collected from a stratified case–control study in the screening phase (1973–1980) and from follow-up of three subcohorts in the follow-up phase (1980–1995). For both phases, MD measurements were only available for about half the…

含潜在永久戒烟状态的随机混合效应模型AI 解读

We develop a mixed model to capture the complex stochastic nature of tobacco abuse and dependence. This model describes transition processes among addiction and nonaddiction stages. An important innovation of our model is allowing an unobserved cure state, or permanent quitting, in contrast to transient quitting. This distinction is necessary to model data from situations where censoring prevents unambiguous determination that a person has been "cured." Moreover, the…

两阶段抽样遗传流行病研究中条件与边际混合设定回归的最大似然推断AI 解读

Summary Two-phase stratified sampling designs can reduce the cost of genetic epidemiologic studies by limiting expensive ascertainments of genetic and environmental exposure to an efficiently selected subsample (phase II) of the main study (phase I). Family history and some covariate information, which may be cheaply gathered for all subjects at phase I, can be used for sampling of informative subjects at phase II. We develop alternative maximum likelihood methods for…

利用基因与环境独立性的病例对照半参数最大似然估计AI 解读

We consider the problem of maximum-likelihood estimation in case-control studies of gene-environment associations with disease when genetic and environmental exposures can be assumed to be independent in the underlying population. Traditional logistic regression analysis may not be efficient in this setting. We study the semiparametric maximum likelihood estimates of logistic regression parameters that exploit the gene-environment independence assumption and leave the…

用于多维疾病分类流行病学研究的两阶段回归模型AI 解读

Polytomous logistic regression is commonly used to analyze epidemiological data with disease subtype information. In this approach effects of exposures on different disease subtypes are studied through separate exposure odds ratios comparing different case groups to the common control group. This article considers the situation where disease subtypes can be defined using multiple characteristics of a disease. For efficient analysis of such data, a two-stage modeling approach…

两阶段抽样回归问题的伪得分估计量AI 解读

Two-phase stratified sampling designs yield efficient estimates of population parameters in regression models while minimizing the costs of data collection. In measurement error problems, for example, error-free covariates are ascertained only for units selected in a validation sample. Estimators proposed heretofore for such designs require all units to have positive probability of being selected. We describe a new semiparametric estimator that relaxes this assumption and…