Within each of the four testing cohorts, genotyping array data was imputed and a genome-wide polygenic score calculated for each individual. Scores were generated by multiplying the genotype dosage of each risk allele for each variant by its respective weight, and then summing across all variants in the score. Incorporating genotype dosages accounts for uncertainty in genotype imputation. Scoring was done using the PLINK2 software program (Chang et al., 2015). Within the UK Biobank, participants were stratified according to decile of the GPS. Average weight and prevalence of severe obesity was determined within each decile. The relationship of high polygenic score, defined as the top decile of the GPS, with severe obesity and treatment with bariatric surgery was next determined in both the UK Biobank and Partners HealthCare system cohorts using logistic regression.
