We examined the combined effects of lead SNPs at the 97 loci in an independent sample of 8,164 European-descent individuals from the Health and Retirement Study17. We observed an average increase of 0.1 BMI units (kg per m2) per BMI-increasing allele, equivalent to 260–320 g for an individual 160–180 cm in height. There was a 1.8 kg per m2 difference in mean BMI between the 145 individuals (1.78%) carrying the most BMI-increasing alleles (>104) and those carrying the mean number of BMI-increasing alleles in the sample (91; Extended Data Fig. 2d), corresponding to a difference of 4.6–5.8 kg for an individual 160–180 cm in height, and a 1.5 kg m−2 difference (3.8–4.9 kg difference) in mean BMI between the 95 individuals (1.16%) carrying the least BMI-increasing alleles (<78) and those carrying the mean number. Such differences are medically significant in predisposing to development of metabolic disease18. For predicting obesity (BMI ≥ 30 kg per m2), adding genetic risk score to a model including age, age squared, sex and four genotype-based principal components slightly, but significantly increases the area under the receiver-operating characteristic curve from 0.576 to 0.601.
