Table 5. Conditional logistic regression analysis including effects of the two-marker haplotype SNPs (rs12970134, rs1943229), the two coding polymorphisms (weight lowering effect: Val103Ile, Ile251Leu) and any other functionally relevant obesity MC4R mutations.
regression modela | non-synonymous MC4R polymorphisms (Val103Ile and Ile251Leu) whose major (wild-type) alleles are associated with obesityb (787 obesity trios) | functionally relevant obesity MC4R mutationsc (525 obesity trios) | |||||||
obesity effect allele | RR for effect allele | 95% CI for RR for effect allele | p-value | obesity effect allele | RR for effect allele | 95% CI for RR for effect allele | p-value | ||
model 1 | rs12970134 | A | 1.45 | 1.21–1.73 | 4.5×10−5 | A | 1.55 | 1.24–1.92 | 8.9×10−5 |
rs1943229 | G | 1.23 | 1.01–1.52 | 0.042 | G | 1.32 | 1.04–1.68 | 0.024 | |
model 2 | MC4R coding region variant | collapsed Val103Ile and Ile251Leu wild-type allele | 1.66 | 1.04–2.63 | 0.032 | collapsed Val103Ile and Ile251Leu wild-type allele | 1.48 | 0.85–2.57 | 0.170 |
collapsed functionally relevant obesity mutationsc mutated allele | 2.57 | 1.07–6.15 | 0.034 | ||||||
model 3 | rs12970134 | A | 1.43 | 1.20–1.71 | 7.9×10−5 | A | 1.52 | 1.22–1.90 | 1.8×10−4 |
rs1943229 | G | 1.24 | 1.01–1.51 | 0.042 | G | 1.30 | 1.02–1.65 | 0.037 | |
MC4R coding region variant | collapsed Val103Ile and Ile251Leu wild-type allele | 1.54 | 0.96–2.48 | 0.073 | collapsed Val103Ile and Ile251Leu wild-type allele | 1.37 | 0.77–2.45 | 0.290 | |
collapsed functionally relevant obesity mutationsc mutated allele | 2.91 | 1.05–8.09 | 0.041 |
model 1 included rs12970134, rs1943229 whereas model 2 included either the non-synonymous MC4R polymorphisms (Val103Ile and Ile251Leu) (left and right panel) or the functionally relevant obesity MC4R mutations (right panel) as one explanatory variables; in model 3, both rs12970134, rs1943229 and the coding variants were included;
wild-type alleles at the non-synonymous MC4R polymorphisms (Val103Ile and Ile251Leu) were combined into one covariable; c mutation alleles Ser30Phe, [Tyr35Stop; 110A>T], Pro78Leu, Ser94Arg, Thr112Met, Ile121Thr, Ser127Leu, Arg165Trp, Ala175Thr, Gly181Asp, Met200Val, Ala244Glu, L211fsX216, Ile317Thr were combined into one covariable; the 525 obesity trios are a subset of all 787 trios for which information on functionally relevant obesity MC4R mutations were available.