Dataset Information

A latent variable partial least squares path modeling approach to regional association and polygenic effect with applications to a human obesity study.

ABSTRACT: Genetic association studies are now routinely used to identify single nucleotide polymorphisms (SNPs) linked with human diseases or traits through single SNP-single trait tests. Here we introduced partial least squares path modeling (PLSPM) for association between single or multiple SNPs and a latent trait that can involve single or multiple correlated measurement(s). Furthermore, the framework naturally provides estimators of polygenic effect by appropriately weighting trait-attributing alleles. We conducted computer simulations to assess the performance via multiple SNPs and human obesity-related traits as measured by body mass index (BMI), waist and hip circumferences. Our results showed that the associate statistics had type I error rates close to nominal level and were powerful for a range of effect and sample sizes. When applied to 12 candidate regions in data (N?=?2,417) from the European Prospective Investigation of Cancer (EPIC)-Norfolk study, a region in FTO was found to have stronger association (rs7204609?rs9939881 at the first intron P?=?4.29×10(-7)) than single SNP analysis (all with P>10(-4)) and a latent quantitative phenotype was obtained using a subset sample of EPIC-Norfolk (N?=?12,559). We believe our method is appropriate for assessment of regional association and polygenic effect on a single or multiple traits.

SUBMITTER: Xue F

PROVIDER: S-EPMC3288051 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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A latent variable partial least squares path modeling approach to regional association and polygenic effect with applications to a human obesity study.

Xue Fuzhong F Li Shengxu S Luan Jian'an J Yuan Zhongshang Z Luben Robert N RN Khaw Kay-Tee KT Wareham Nicholas J NJ Loos Ruth J F RJ Zhao Jing Hua JH

PloS one 20120227 2

Genetic association studies are now routinely used to identify single nucleotide polymorphisms (SNPs) linked with human diseases or traits through single SNP-single trait tests. Here we introduced partial least squares path modeling (PLSPM) for association between single or multiple SNPs and a latent trait that can involve single or multiple correlated measurement(s). Furthermore, the framework naturally provides estimators of polygenic effect by appropriately weighting trait-attributing alleles ...[more]

PMID: 22384102

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Project description:BACKGROUND:Recent technological developments have enabled the measurement of a plethora of biomolecular data from various omics domains, and research is ongoing on statistical methods to leverage these omics data to better model and understand biological pathways and genetic architectures of complex phenotypes. Current reviews report that the simultaneous analysis of multiple (i.e. three or more) high dimensional omics data sources is still challenging and suitable statistical methods are unavailable. Often mentioned challenges are the lack of accounting for the hierarchical structure between omics domains and the difficulty of interpretation of genomewide results. This study is motivated to address these challenges. We propose multiset sparse Partial Least Squares path modeling (msPLS), a generalized penalized form of Partial Least Squares path modeling, for the simultaneous modeling of biological pathways across multiple omics domains. msPLS simultaneously models the effect of multiple molecular markers, from multiple omics domains, on the variation of multiple phenotypic variables, while accounting for the relationships between data sources, and provides sparse results. The sparsity in the model helps to provide interpretable results from analyses of hundreds of thousands of biomolecular variables. RESULTS:With simulation studies, we quantified the ability of msPLS to discover associated variables among high dimensional data sources. Furthermore, we analysed high dimensional omics datasets to explore biological pathways associated with Marfan syndrome and with Chronic Lymphocytic Leukaemia. Additionally, we compared the results of msPLS to the results of Multi-Omics Factor Analysis (MOFA), which is an alternative method to analyse this type of data. CONCLUSIONS:msPLS is an multiset multivariate method for the integrative analysis of multiple high dimensional omics data sources. It accounts for the relationship between multiple high dimensional data sources while it provides interpretable results through its sparse solutions. The biomarkers found by msPLS in the omics datasets can be interpreted in terms of biological pathways associated with the pathophysiology of Marfan syndrome and of Chronic Lymphocytic Leukaemia. Additionally, msPLS outperforms MOFA in terms of variation explained in the chronic lymphocytic leukaemia dataset while it identifies the two most important clinical markers for Chronic Lymphocytic Leukaemia AVAILABILITY: http://uva.csala.me/mspls.https://github.com/acsala/2018_msPLS.

Project description:Interest in improving advertisement impact on potential consumers has increased recently. One well-known strategy is to use emotion-based advertisement. In this approach, an emotional link with consumers is created, aiming to enhance the memorization process. In recent years, Neuromarketing techniques have allowed us to obtain more objective information on this process. However, the role of the autonomic nervous system (ANS) in the memorization process using emotional advertisement still needs further research. In this work, we propose the use of two physiological signals, namely, an electrocardiogram (heart rate variability, HRV) and electrodermal activity (EDA), to obtain indices assessing the ANS. We measured these signals in 43 subjects during the observation of six different spots, each conveying a different emotion (rational, disgust, anger, surprise, and sadness). After observing the spots, subjects were asked to answer a questionnaire to measure the spontaneous and induced recall. We propose the use of a statistical data-driven model based on Partial Least Squares-Path Modeling (PSL-PM), which allows us to incorporate contextual knowledge by defining a relational graph of unobservable variables (latent variables, LV), which are, in turn, estimated by measured variables (indices of the ANS). We defined four LVs, namely, sympathetic, vagal, ANS, and recall. Sympathetic and vagal are connected to the ANS, the latter being a measure of recall, estimated from a questionnaire. The model is then fitted to the data. Results showed that vagal activity (described by HRV indices) is the most critical factor to describe ANS activity; they are inversely related except for the spot, which is mainly rational. The model captured a moderate-to-high variability of ANS behavior, ranging from 38% up to 64% of the explained variance of the ANS. However, it can explain at most 11% of the recall score of the subjects. The proposed approach allows for the easy inclusion of more physiological measurements and provides an easy-to-interpret model of the ANS response to emotional advertisement.

Dataset Information

A latent variable partial least squares path modeling approach to regional association and polygenic effect with applications to a human obesity study.

Publications

A latent variable partial least squares path modeling approach to regional association and polygenic effect with applications to a human obesity study.

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