Machine Learning Prediction of Biomarkers from SNPs and of Disease Risk from Biomarkers in the UK Biobank

Author:

Widen Erik,Raben Timothy G.ORCID,Lello Louis,Hsu Stephen D.H.

Abstract

AbstractWe use UK Biobank data to train predictors for 48 blood and urine markers such as HDL, LDL, lipoprotein A, glycated haemoglobin, … from SNP genotype. For example, our predictor correlates ∼ 0.76 with lipoprotein A level, which is highly heritable and an independent risk factor for heart disease. This may be the most accurate genomic prediction of a quantitative trait that has yet been produced (specifically, for European ancestry groups). We also train predictors of common disease risk using blood and urine biomarkers alone (no DNA information). Individuals who are at high risk (e.g., odds ratio of > 5x population average) can be identified for conditions such as coronary artery disease (AUC ∼ 0.75), diabetes (AUC ∼ 0.95), hypertension, liver and kidney problems, and cancer using biomarkers alone. Our atherosclerotic cardiovascular disease (ASCVD) predictor uses ∼ 10 biomarkers and performs in UKB evaluation as well as or better than the American College of Cardiology ASCVD Risk Estimator, which uses quite different inputs (age, diagnostic history, BMI, smoking status, statin usage, etc.). We compare polygenic risk scores (risk conditional on genotype: (risk score | SNPs)) for common diseases to the risk predictors which result from the concatenation of learned functions (risk score | biomarkers) and (biomarker | SNPs).

Publisher

Cold Spring Harbor Laboratory

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