Dataset Information

Flexible Locally Weighted Penalized Regression With Applications on Prediction of Alzheimer's Disease Neuroimaging Initiative's Clinical Scores.

ABSTRACT: In recent years, we have witnessed the explosion of large-scale data in various fields. Classical statistical methodologies, such as linear regression or generalized linear regression, often show inadequate performance on heterogeneous data because the key homogeneity assumption fails. In this paper, we present a flexible framework to handle heterogeneous populations that can be naturally grouped into several ordered subtypes. A local model technique utilizing ordinal class labels during the training stage is proposed. We define a new "progression score" that captures the progression of ordinal classes, and use a truncated Gaussian kernel to construct the weight function in a local regression framework. Furthermore, given the weights, we apply sparse shrinkage on the local fitting to handle high dimensionality. In this way, our local model is able to conduct variable selection on each query point. Numerical studies show the superiority of our proposed method over several existing ones. Our method is also applied to the Alzheimer's Disease Neuroimaging Initiative data to make predictions on the longitudinal clinical scores based on different modalities of baseline brain image features.

SUBMITTER: Wang P

PROVIDER: S-EPMC7388691 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Publications

Flexible Locally Weighted Penalized Regression With Applications on Prediction of Alzheimer's Disease Neuroimaging Initiative's Clinical Scores.

Wang Peiyao P Liu Yufeng Y Shen Dinggang D

IEEE transactions on medical imaging 20181205 6

In recent years, we have witnessed the explosion of large-scale data in various fields. Classical statistical methodologies, such as linear regression or generalized linear regression, often show inadequate performance on heterogeneous data because the key homogeneity assumption fails. In this paper, we present a flexible framework to handle heterogeneous populations that can be naturally grouped into several ordered subtypes. A local model technique utilizing ordinal class labels during the tra ...[more]

PMID: 30530315

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Project description:Polygenic Risk Scores (PRS) combine genotype information across many single-nucleotide polymorphisms (SNPs) to give a score reflecting the genetic risk of developing a disease. PRS might have a major impact on public health, possibly allowing for screening campaigns to identify high-genetic risk individuals for a given disease. The "Clumping+Thresholding" (C+T) approach is the most common method to derive PRS. C+T uses only univariate genome-wide association studies (GWAS) summary statistics, which makes it fast and easy to use. However, previous work showed that jointly estimating SNP effects for computing PRS has the potential to significantly improve the predictive performance of PRS as compared to C+T. In this paper, we present an efficient method for the joint estimation of SNP effects using individual-level data, allowing for practical application of penalized logistic regression (PLR) on modern datasets including hundreds of thousands of individuals. Moreover, our implementation of PLR directly includes automatic choices for hyper-parameters. We also provide an implementation of penalized linear regression for quantitative traits. We compare the performance of PLR, C+T and a derivation of random forests using both real and simulated data. Overall, we find that PLR achieves equal or higher predictive performance than C+T in most scenarios considered, while being scalable to biobank data. In particular, we find that improvement in predictive performance is more pronounced when there are few effects located in nearby genomic regions with correlated SNPs; for instance, in simulations, AUC values increase from 83% with the best prediction of C+T to 92.5% with PLR. We confirm these results in a data analysis of a case-control study for celiac disease where PLR and the standard C+T method achieve AUC values of 89% and of 82.5%. Applying penalized linear regression to 350,000 individuals of the UK Biobank, we predict height with a larger correlation than with the best prediction of C+T (∼65% instead of ∼55%), further demonstrating its scalability and strong predictive power, even for highly polygenic traits. Moreover, using 150,000 individuals of the UK Biobank, we are able to predict breast cancer better than C+T, fitting PLR in a few minutes only. In conclusion, this paper demonstrates the feasibility and relevance of using penalized regression for PRS computation when large individual-level datasets are available, thanks to the efficient implementation available in our R package bigstatsr.

Dataset Information

Flexible Locally Weighted Penalized Regression With Applications on Prediction of Alzheimer's Disease Neuroimaging Initiative's Clinical Scores.

Publications

Flexible Locally Weighted Penalized Regression With Applications on Prediction of Alzheimer's Disease Neuroimaging Initiative's Clinical Scores.

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