PubMed Health⌕ Search

PubMed · 12855073

A finite mixture distribution model for data collected from twins.

Abstract

Most analyses of data collected from a classical twin study of monozygotic (MZ) and dizygotic (DZ) twins assume that zygosity has been diagnosed without error. However, large scale surveys frequently resort to questionnaire-based methods of diagnosis which classify twins as MZ or DZ with less than perfect accuracy. This article describes a mixture distribution approach to the analysis of twin data when zygosity is not perfectly diagnosed. Estimates of diagnostic accuracy are used to weight the likelihood of the data according to the probability that any given pair is either MZ or DZ. The performance of this method is compared to fully accurate diagnosis, and to the analysis of samples that include some misclassified pairs. Conventional analysis of samples containing misclassified pairs yields biased estimates of variance components, such that additive genetic variance (A) is underestimated while common environment (C) and specific environment (E) components are overestimated. The bias is non-trivial; for 10% misclassification, true values of Additive genetic: Common environment: Specific Environment variance components of.6:.2:.2 are estimated as.48:.29:.23, respectively. The mixture distribution yields unbiased estimates, while showing relatively little loss of statistical precision for misclassification rates of 15% or less. The method is shown to perform quite well even when no information on zygosity is available, and may be applied when pair-specific estimates of zygosity probabilities are available.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Michael C Neale. 2003. A finite mixture distribution model for data collected from twins.. https://doi.org/10.1375/136905203765693898

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Global Genomic Surveillance.

Global genomic surveillance has emerged as a foundational pillar of public health in the twenty-first century, enabling real-time tracking of pathogen evolution and informing outbreak response. This chapter examines the strategic architecture of global genomic surveillance, focusing on its application to arboviruses such as chikungunya virus (CHIKV). It explores the integration of genomic data with epidemiological, clinical, and environmental information within a One Health framework, while addressing critical challenges in governance, equity, and interoperability. The discussion covers the entire genomic surveillance workflow, from sample collection and sequencing to bioinformatic analysis and phylogenetic inference, and highlights the transformative role of artificial intelligence (AI) in predictive surveillance. By analyzing global initiatives, operational barriers, and emerging technologies, this chapter underscores the necessity of sustainable, equitable, and interoperable genomic systems to proactively address current and future infectious disease threats.

Humans↗

Systematic Dissection of Key Driver Perturbation Signatures in Single Cells via ECCITE-seq.

CRISPR screens, such as expanded CRISPR-compatible cellular indexing of transcriptomes and epitopes by sequencing (ECCITE-seq), enable the simultaneous measurement of transcriptomes, gRNA identity, and cell-surface protein expression at single-cell resolution to systematically interrogate gene function. This platform provides a powerful and scalable experimental approach for validating disease-associated regulators identified by large-scale association studies and other computational methods, including network-based analyses of multi-omics data. Here, as an example application, we describe an ECCITE-seq framework to characterize the transcriptomic consequences of perturbing multiple neuronal key driver genes associated with Alzheimer's disease (AD) in human-induced pluripotent stem cell (hiPSC)-derived neurons. More broadly, by integrating customized pooled gRNA libraries with different CRISPR effectors across multiple cell types, this approach allows for the assessment of the regulatory impact of candidate genes implicated in development and disease processes.

Humans↗

Identification of Genome-Wide Chromatin Structural Aberration in Cancer by Hi-C Analysis.

Aberrant three-dimensional genome organization is a hallmark of cancer, often driving oncogene activation through mechanisms such as enhancer hijacking. High-throughput chromosome conformation capture (Hi-C) maps these interactions on a genome-wide scale. Unlike earlier dilution-based methods, in situ Hi-C performs proximity ligation within intact nuclei, minimizing random ligation noise and enabling fine-scale structure detection. This chapter describes an optimized in situ Hi-C protocol tailored for cancer cell lines using MboI digestion and biotin-mediated pull-down to generate high-complexity libraries. We further outline a computational workflow that extends beyond standard topological mapping of compartments and topologically associating domains to identify cancer-specific aberrations. Specifically, we focus on detecting chromosomal rearrangements (structural variants) and characterizing the distinct circular topology of extrachromosomal DNA. This integrated experimental and analytical framework provides the necessary tools to dissect the spatial dysregulation underlying tumor evolution.

Humans↗