Large-scale genome-wide association studies (GWAS) have offered an exciting opportunity to discover putative causal genes or risk factors associated with diseases by using SNPs as instrumental variables (IVs). However, conventional approaches assume linear causal relations partly for simplicity and partly for the only availability of GWAS summary data. In this work, we propose a novel model {for transcriptome-wide association studies (TWAS)} to incorporate nonlinear relationships across IVs, an exposure, and an outcome, which is robust against violations of the valid IV assumptions and permits the use of GWAS summary data. We decouple the estimation of a marginal causal effect and a nonlinear transformation, where the former is estimated via sliced inverse regression and a sparse instrumental variable regression, and the latter is estimated by a ratio-adjusted inverse regression. On this ground, we propose an inferential procedure. An application of the proposed method to the ADNI gene expression data and the IGAP GWAS summary data identifies 18 causal genes associated with Alzheimer's disease, including APOE and TOMM40, in addition to 7 other genes missed by two-stage least squares considering only linear relationships. Our findings suggest that nonlinear modeling is required to unleash the power of IV regression for identifying potentially nonlinear gene-trait associations. Accompanying this paper is our Python library nl-causal(//github.com/nl-causal/nonlinear-causal) that implements the proposed method.
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The nonnegative garrote (NNG) is among the first approaches that combine variable selection and shrinkage of regression estimates. When more than the derivation of a predictor is of interest, NNG has some conceptual advantages over the popular lasso. Nevertheless, NNG has received little attention. The original NNG relies on least-squares (OLS) estimates, which are highly variable in data with a high degree of multicollinearity (HDM) and do not exist in high-dimensional data (HDD). This might be the reason that NNG is not used in such data. Alternative initial estimates have been proposed but hardly used in practice. Analyzing three structurally different data sets, we demonstrated that NNG can also be applied in HDM and HDD and compared its performance with the lasso, adaptive lasso, relaxed lasso, and best subset selection in terms of variables selected, regression estimates, and prediction. Replacing OLS by ridge initial estimates in HDM and lasso initial estimates in HDD helped NNG select simpler models than competing approaches without much increase in prediction errors. Simpler models are easier to interpret, an important issue for descriptive modelling. Based on the limited experience from three datasets, we assume that the NNG can be a suitable alternative to the lasso and its extensions. Neutral comparison simulation studies are needed to better understand the properties of variable selection methods, compare them and derive guidance for practice.
The method of instrumental variables provides a fundamental and practical tool for causal inference in many empirical studies where unmeasured confounding between the treatments and the outcome is present. Modern data such as the genetical genomics data from these studies are often high-dimensional. The high-dimensional linear instrumental-variables regression has been considered in the literature due to its simplicity albeit a true nonlinear relationship may exist. We propose a more data-driven approach by considering the nonparametric additive models between the instruments and the treatments while keeping a linear model between the treatments and the outcome so that the coefficients therein can directly bear causal interpretation. We provide a two-stage framework for estimation and inference under this more general setup. The group lasso regularization is first employed to select optimal instruments from the high-dimensional additive models, and the outcome variable is then regressed on the fitted values from the additive models to identify and estimate important treatment effects. We provide non-asymptotic analysis of the estimation error of the proposed estimator. A debiasing procedure is further employed to yield valid inference. Extensive numerical experiments show that our method can rival or outperform existing approaches in the literature. We finally analyze the mouse obesity data and discuss new findings from our method.
Root causal analysis seeks to identify the set of initial perturbations that induce an unwanted outcome. In prior work, we defined sample-specific root causes of disease using exogenous error terms that predict a diagnosis in a structural equation model. We rigorously quantified predictivity using Shapley values. However, the associated algorithms for inferring root causes assume no latent confounding. We relax this assumption by permitting confounding among the predictors. We then introduce a corresponding procedure called Extract Errors with Latents (EEL) for recovering the error terms up to contamination by vertices on certain paths under the linear non-Gaussian acyclic model. EEL also identifies the smallest sets of dependent errors for fast computation of the Shapley values. The algorithm bypasses the hard problem of estimating the underlying causal graph in both cases. Experiments highlight the superior accuracy and robustness of EEL relative to its predecessors.
Neyman (1923/1990) introduced the randomization model, which contains the notation of potential outcomes to define causal effects and a framework for large-sample inference based on the design of the experiment. However, the existing theory for this framework is far from complete especially when the number of treatment levels diverges and the group sizes vary a lot across treatment levels. We provide a unified discussion of statistical inference under the randomization model with general group sizes across treatment levels. We formulate the estimator in terms of a linear permutational statistic and use results based on Stein's method to derive various Berry--Esseen bounds on the linear and quadratic functions of the estimator. These new Berry--Esseen bounds serve as basis for design-based causal inference with possibly diverging treatment levels and diverging dimension of causal effects. We also fill an important gap by proposing novel variance estimators for experiments with possibly many treatment levels without replications. Equipped with the newly developed results, design-based causal inference in general settings becomes more convenient with stronger theoretical guarantees.
We introduce two synthetic likelihood methods for Simulation-Based Inference (SBI), to conduct either amortized or targeted inference from experimental observations when a high-fidelity simulator is available. Both methods learn a conditional energy-based model (EBM) of the likelihood using synthetic data generated by the simulator, conditioned on parameters drawn from a proposal distribution. The learned likelihood can then be combined with any prior to obtain a posterior estimate, from which samples can be drawn using MCMC. Our methods uniquely combine a flexible Energy-Based Model and the minimization of a KL loss: this is in contrast to other synthetic likelihood methods, which either rely on normalizing flows, or minimize score-based objectives; choices that come with known pitfalls. Our first method, Amortized Unnormalized Neural Likelihood Estimation (AUNLE), introduces a tilting trick during training that allows to significantly lower the computational cost of inference by enabling the use of efficient MCMC techniques. Our second method, Sequential UNLE (SUNLE), employs a robust doubly intractable approach in order to re-use simulation data and improve posterior accuracy on a specific dataset. We demonstrate the properties of both methods on a range of synthetic datasets, and apply them to a neuroscience model of the pyloric network in the crab Cancer Borealis, matching the performance of other synthetic likelihood methods at a fraction of the simulation budget.
Machine learning (ML) models are costly to train as they can require a significant amount of data, computational resources and technical expertise. Thus, they constitute valuable intellectual property that needs protection from adversaries wanting to steal them. Ownership verification techniques allow the victims of model stealing attacks to demonstrate that a suspect model was in fact stolen from theirs. Although a number of ownership verification techniques based on watermarking or fingerprinting have been proposed, most of them fall short either in terms of security guarantees (well-equipped adversaries can evade verification) or computational cost. A fingerprinting technique introduced at ICLR '21, Dataset Inference (DI), has been shown to offer better robustness and efficiency than prior methods. The authors of DI provided a correctness proof for linear (suspect) models. However, in the same setting, we prove that DI suffers from high false positives (FPs) -- it can incorrectly identify an independent model trained with non-overlapping data from the same distribution as stolen. We further prove that DI also triggers FPs in realistic, non-linear suspect models. We then confirm empirically that DI leads to FPs, with high confidence. Second, we show that DI also suffers from false negatives (FNs) -- an adversary can fool DI by regularising a stolen model's decision boundaries using adversarial training, thereby leading to an FN. To this end, we demonstrate that DI fails to identify a model adversarially trained from a stolen dataset -- the setting where DI is the hardest to evade. Finally, we discuss the implications of our findings, the viability of fingerprinting-based ownership verification in general, and suggest directions for future work.
Causal learning has long concerned itself with the accurate recovery of underlying causal mechanisms. Such causal modelling enables better explanations of out-of-distribution data. Prior works on causal learning assume that the high-level causal variables are given. However, in machine learning tasks, one often operates on low-level data like image pixels or high-dimensional vectors. In such settings, the entire Structural Causal Model (SCM) -- structure, parameters, \textit{and} high-level causal variables -- is unobserved and needs to be learnt from low-level data. We treat this problem as Bayesian inference of the latent SCM, given low-level data. For linear Gaussian additive noise SCMs, we present a tractable approximate inference method which performs joint inference over the causal variables, structure and parameters of the latent SCM from random, known interventions. Experiments are performed on synthetic datasets and a causally generated image dataset to demonstrate the efficacy of our approach. We also perform image generation from unseen interventions, thereby verifying out of distribution generalization for the proposed causal model.
The concept of causality plays an important role in human cognition . In the past few decades, causal inference has been well developed in many fields, such as computer science, medicine, economics, and education. With the advancement of deep learning techniques, it has been increasingly used in causal inference against counterfactual data. Typically, deep causal models map the characteristics of covariates to a representation space and then design various objective optimization functions to estimate counterfactual data unbiasedly based on the different optimization methods. This paper focuses on the survey of the deep causal models, and its core contributions are as follows: 1) we provide relevant metrics under multiple treatments and continuous-dose treatment; 2) we incorporate a comprehensive overview of deep causal models from both temporal development and method classification perspectives; 3) we assist a detailed and comprehensive classification and analysis of relevant datasets and source code.
This paper focuses on the expected difference in borrower's repayment when there is a change in the lender's credit decisions. Classical estimators overlook the confounding effects and hence the estimation error can be magnificent. As such, we propose another approach to construct the estimators such that the error can be greatly reduced. The proposed estimators are shown to be unbiased, consistent, and robust through a combination of theoretical analysis and numerical testing. Moreover, we compare the power of estimating the causal quantities between the classical estimators and the proposed estimators. The comparison is tested across a wide range of models, including linear regression models, tree-based models, and neural network-based models, under different simulated datasets that exhibit different levels of causality, different degrees of nonlinearity, and different distributional properties. Most importantly, we apply our approaches to a large observational dataset provided by a global technology firm that operates in both the e-commerce and the lending business. We find that the relative reduction of estimation error is strikingly substantial if the causal effects are accounted for correctly.
Causal inference is a critical research topic across many domains, such as statistics, computer science, education, public policy and economics, for decades. Nowadays, estimating causal effect from observational data has become an appealing research direction owing to the large amount of available data and low budget requirement, compared with randomized controlled trials. Embraced with the rapidly developed machine learning area, various causal effect estimation methods for observational data have sprung up. In this survey, we provide a comprehensive review of causal inference methods under the potential outcome framework, one of the well known causal inference framework. The methods are divided into two categories depending on whether they require all three assumptions of the potential outcome framework or not. For each category, both the traditional statistical methods and the recent machine learning enhanced methods are discussed and compared. The plausible applications of these methods are also presented, including the applications in advertising, recommendation, medicine and so on. Moreover, the commonly used benchmark datasets as well as the open-source codes are also summarized, which facilitate researchers and practitioners to explore, evaluate and apply the causal inference methods.
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