FTO and obesity due to melanocortin 4 receptor deficiency: While earlier large-scale GWAS and meta-analyses have primarily and robustly linked FTO variants to elevated BMI and obesity risk (Frayling et al., 2007; Quan et al., 2015), our mediation analysis demonstrates that a substantial portion of MetS risk is attributable to dyslipidemia and hyperglycemia, partially independent of absolute adiposity measures.