A recently published genome-wide association study (GWAS) quantified the relationship between each of 2.1 million common genetic variants and BMI in over 300,000 individuals (Locke et al., 2015). None of the individual variants accounts for a large proportion of the phenotype. The strongest association was noted for a common variant at the FTO locus: the risk allele was associated with a statistically robust, but clinically modest, increase in weight of approximately 1 kilogram per inherited risk allele. Obtaining meaningful predictive power thus requires aggregating information from many common variants into a polygenic score (Chatterjee et al., 2016; Khera et al., 2018a). However, previous efforts to create an effective polygenic score for obesity have had only modest success (Loos and Janssens, 2017).
