Chunk #12 — Results — Impact of ascertainment strategy on discovered and known loci — Effect of loci previously identified in extremely obese samples in our study
Previous studies of extreme childhood and/or adult obesity using different ascertainment strategies have reported genome-wide significant or near genome-wide significant associations (P<5×10-7) with FTO, MC4R, TMEM18, FAIM2, TNKS, HOXB5, OLFM4, NPC1, MAF, PTER, SDCCAG8, PCSK1 (rs6235 and rs6232) and KCNMA1.14-16,22-26 With the exception of PCSK1 (rs6232) for tails of BMI and MAF for tails of BMI and obesity class II, all associations showed consistent directions of effect across the BMI-related outcomes (Supplementary Table 11). Of the 13 loci, replication at a significance level of P<0.004 (Bonferroni-corrected) was observed for four SNPs (FTO, MC4R, TMEM18, FAIM2) for the tails of BMI and all clinical classes of obesity Two loci, MAF and KCNMA1, which have thus far only been reported for extreme obesity, were not significantly associated with any of our traits at either a Bonferroni-corrected or nominal significance threshold (P<0.05).
