We estimated the combined impact of the 16 loci associated with FG (the 14 loci included in the genotype score plus TCF7L2 and SLC30A8) in some of the largest cohorts (Framingham, NFBC 1966 and ARIC) by constructing a genotype score equal to the sum of the expected number of risk alleles at each SNP weighted by their effect sizes (see Online Methods). FG levels were higher in individuals with higher genotype scores (Figure 3), with mean differences of ~0.4 mmol/L (5.93 vs 5.51 mmol/L in NFBC 1966; 5.36 vs 5.03 mmol/L in Framingham; 5.70 vs 5.29 mmol/L in ARIC) comparing individuals with a score of 23 or higher (5.6% of the sample) to those with a genotype score of 12 or lower (2.9% of the sample). The 0.4 mmol/L (7.2 mg/dl) difference between the two tails of the distribution of risk score in the population (top 5.6% vs bottom 2.9%) is of clinical relevance, as it represents a shift of approximately 25 centile points in the distribution of FG. Prospective evidence has shown that a difference of this magnitude in
