Finally, it is quite clear that the effect sizes required for deeming SNPs statistically significant are somewhat unrealistic. For example, in Fig. 4, many SNPs have slopes that exceed 2, and an increase from zero to two risk alleles would involve a four-unit increase in BMI. For a 140-pound adult who is 5′8″, this increase translates to an increase in of more than 26 pounds. This assumes an additive model and doesn't take into account the minor allele frequency, but it illustrates the rather extreme substantive implications if our understanding of genetic influences on BMI is based on SNPs that are deemed to be statistically significant from GWAS models. The same (albeit more extreme) understanding can be seen for the SNPs in the upper-left corner of Fig. 4 that have slopes that are near or exceed 10; a 20-BMI increase comparing the two homozygous groups at one loci is simply not possible.
