We use UK Biobank data to train predictors for 65 blood and urine markers such as HDL, LDL, lipoprotein A, glycated haemoglobin, etc. from SNP genotype. For example, our Polygenic Score (PGS) 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); we call these predictors biomarker risk scores, BMRS. Individuals who are at high risk (e.g., odds ratio of >5× 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: PRS) for common diseases to the risk predictors which result from the concatenation of learned functions BMRS and PGS, i.e., applying the BMRS predictors to the PGS output.

We construct a polygenic health index as a weighted sum of polygenic risk scores for 20 major disease conditions, including, e.g., coronary artery disease, type 1 and 2 diabetes, schizophrenia, etc. Individual weights are determined by population-level estimates of impact on life expectancy. We validate this index in odds ratios and selection experiments using unrelated individuals and siblings (pairs and trios) from the UK Biobank. Individuals with higher index scores have decreased disease risk across almost all 20 diseases (no significant risk increases), and longer calculated life expectancy. When estimated Disability Adjusted Life Years (DALYs) are used as the performance metric, the gain from selection among ten individuals (highest index score vs average) is found to be roughly 4 DALYs. We find no statistical evidence for antagonistic trade-offs in risk reduction across these diseases. Correlations between genetic disease risks are found to be mostly positive and generally mild. These results have important implications for public health and also for fundamental issues such as pleiotropy and genetic architecture of human disease conditions.

We generalize earlier results on one-point functions in \( \mathcal{N}=4 \) SYM with a codimension one defect, dual to the D3-D5-brane setup in type IIB string theory on AdS₅ ×S⁵, to a similar setup in the β-deformed version of the theory. The treelevel vacuum expectation values of single-trace operators in the two-scalar-subsector are expressed as overlaps between a matrix product state (MPS) and Bethe states in the corresponding twisted spin-chain picture. We comment on the properties of this MPS and present the simplest analytical overlaps and their behavior in a certain limit (of large k). Importantly, we note that the deformation alters earlier interpretations of the MPS as an integrable boundary state, seemingly obstructing simplifications of the overlaps analogous to the compact determinant formula found in the non-deformed theory. The results are supplemented with some supporting numerical results for operators of length eight with four excitations.

We 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).

We construct a polygenic health index as a weighted sum of polygenic risk scores for 20 major disease conditions, including, e.g., coronary artery disease, type 1 and 2 diabetes, schizophrenia, etc. Individual weights are determined by population-level estimates of impact on life expectancy. We validate this index in odds ratios and selection experiments using unrelated individuals and siblings (pairs and trios) from the UK Biobank. Individuals with higher index scores have decreased disease risk across almost all 20 diseases (no significant risk increases), and longer calculated life expectancy. When estimated Disability Adjusted Life Years (DALYs) are used as the performance metric, the gain from selection among 10 individuals (highest index score vs average) is found to be roughly 4 DALYs. We find no statistical evidence for antagonistic trade-offs in risk reduction across these diseases. Correlations between genetic disease risks are found to be mostly positive and generally mild. These results have important implications for public health and also for fundamental issues such as pleiotropy and genetic architecture of human disease conditions.