Dataset Information

Ancestry may confound genetic machine learning: Candidate-gene prediction of opioid use disorder as an example.

ABSTRACT:

Background

Machine learning (ML) models are beginning to proliferate in psychiatry, however machine learning models in psychiatric genetics have not always accounted for ancestry. Using an empirical example of a proposed genetic test for OUD, and exploring a similar test for tobacco dependence and a simulated binary phenotype, we show that genetic prediction using ML is vulnerable to ancestral confounding.

Methods

We utilize five ML algorithms trained with 16 brain reward-derived "candidate" SNPs proposed for commercial use and examine their ability to predict OUD vs. ancestry in an out-of-sample test set (N = 1000, stratified into equal groups of n = 250 cases and controls each of European and African ancestry). We rerun analyses with 8 random sets of allele-frequency matched SNPs. We contrast findings with 11 genome-wide significant variants for tobacco smoking. To document generalizability, we generate and test a random phenotype.

Results

None of the 5 ML algorithms predict OUD better than chance when ancestry was balanced but were confounded with ancestry in an out-of-sample test. In addition, the algorithms preferentially predicted admixed subpopulations. Random sets of variants matched to the candidate SNPs by allele frequency produced similar bias. Genome-wide significant tobacco smoking variants were also confounded by ancestry. Finally, random SNPs predicting a random simulated phenotype show that the bias attributable to ancestral confounding could impact any ML-based genetic prediction.

Conclusions

Researchers and clinicians are encouraged to be skeptical of claims of high prediction accuracy from ML-derived genetic algorithms for polygenic traits like addiction, particularly when using candidate variants.

SUBMITTER: Hatoum AS

PROVIDER: S-EPMC9358969 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

Ancestry may confound genetic machine learning: Candidate-gene prediction of opioid use disorder as an example.

Hatoum Alexander S AS Wendt Frank R FR Galimberti Marco M Polimanti Renato R Neale Benjamin B Kranzler Henry R HR Gelernter Joel J Edenberg Howard J HJ Agrawal Arpana A

Drug and alcohol dependence 20211009 Pt B

<h4>Background</h4>Machine learning (ML) models are beginning to proliferate in psychiatry, however machine learning models in psychiatric genetics have not always accounted for ancestry. Using an empirical example of a proposed genetic test for OUD, and exploring a similar test for tobacco dependence and a simulated binary phenotype, we show that genetic prediction using ML is vulnerable to ancestral confounding.<h4>Methods</h4>We utilize five ML algorithms trained with 16 brain reward-derived ...[more]

PMID: 34710714

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Project description:BackgroundOpioid use disorder (OUD) is a critical public health crisis in the United States, affecting >5.5 million Americans in 2021. Machine learning has been used to predict patient risk of incident OUD. However, little is known about the fairness and bias of these predictive models.ObjectiveThe aims of this study are two-fold: (1) to develop a machine learning bias mitigation algorithm for sociodemographic features and (2) to develop a fairness-aware weighted majority voting (WMV) classifier for OUD prediction.MethodsWe used the 2020 National Survey on Drug and Health data to develop a neural network (NN) model using stochastic gradient descent (SGD; NN-SGD) and an NN model using Adam (NN-Adam) optimizers and evaluated sociodemographic bias by comparing the area under the curve values. A bias mitigation algorithm, based on equality of odds, was implemented to minimize disparities in specificity and recall. Finally, a WMV classifier was developed for fairness-aware prediction of OUD. To further analyze bias detection and mitigation, we did a 1-N matching of OUD to non-OUD cases, controlling for socioeconomic variables, and evaluated the performance of the proposed bias mitigation algorithm and WMV classifier.ResultsOur bias mitigation algorithm substantially reduced bias with NN-SGD, by 21.66% for sex, 1.48% for race, and 21.04% for income, and with NN-Adam by 16.96% for sex, 8.87% for marital status, 8.45% for working condition, and 41.62% for race. The fairness-aware WMV classifier achieved a recall of 85.37% and 92.68% and an accuracy of 58.85% and 90.21% using NN-SGD and NN-Adam, respectively. The results after matching also indicated remarkable bias reduction with NN-SGD and NN-Adam, respectively, as follows: sex (0.14% vs 0.97%), marital status (12.95% vs 10.33%), working condition (14.79% vs 15.33%), race (60.13% vs 41.71%), and income (0.35% vs 2.21%). Moreover, the fairness-aware WMV classifier achieved high performance with a recall of 100% and 85.37% and an accuracy of 73.20% and 89.38% using NN-SGD and NN-Adam, respectively.ConclusionsThe application of the proposed bias mitigation algorithm shows promise in reducing sociodemographic bias, with the WMV classifier confirming bias reduction and high performance in OUD prediction.

Project description:BackgroundOpioid Use Disorder (OUD) and opioid overdose (OD) impose huge social and economic burdens on society and health care systems. Research suggests that Medication for Opioid Use Disorder (MOUD) is effective in the treatment of OUD. We use machine learning to investigate the association between patient's adherence to prescribed MOUD along with other risk factors in patients diagnosed with OUD and potential OD following the treatment.MethodsWe used longitudinal Medicaid claims for two selected US states to subset a total of 26,685 patients with OUD diagnosis and appropriate Medicaid coverage between 2015 and 2018. We considered patient age, sex, region level socio-economic data, past comorbidities, MOUD prescription type and other selected prescribed medications along with the Proportion of Days Covered (PDC) as a proxy for adherence to MOUD as predictive variables for our model, and overdose events as the dependent variable. We applied four different machine learning classifiers and compared their performance, focusing on the importance and effect of PDC as a variable. We also calculated results based on risk stratification, where our models separate high risk individuals from low risk, to assess usefulness in clinical decision-making.ResultsAmong the selected classifiers, the XGBoost classifier has the highest AUC (0.77) closely followed by the Logistic Regression (LR). The LR has the best stratification result: patients in the top 10% of risk scores account for 35.37% of overdose events over the next 12 month observation period. PDC score calculated over the treatment window is one of the most important features, with better PDC lowering risk of OD, as expected. In terms of risk stratification results, of the 35.37% of overdose events that the predictive model could detect within the top 10% of risk scores, 72.3% of these cases were non-adherent in terms of their medication (PDC <0.8). Targeting the top 10% outcome of the predictive model could decrease the total number of OD events by 10.4%.ConclusionsThe best performing models allow identification of, and focus on, those at high risk of opioid overdose. With MOUD being included for the first time as a factor of interest, and being identified as a significant factor, outreach activities related to MOUD can be targeted at those at highest risk.

Dataset Information

Ancestry may confound genetic machine learning: Candidate-gene prediction of opioid use disorder as an example.

Background

Methods

Results

Conclusions

Publications

Ancestry may confound genetic machine learning: Candidate-gene prediction of opioid use disorder as an example.

Similar Datasets

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