Is the adiposity‐associated <scp><i>FTO</i></scp> gene variant related to all‐cause mortality independent of adiposity? Meta‐analysis of data from 169,551 <scp>C</scp>aucasian adults

Summary Previously, a single nucleotide polymorphism ( SNP ), rs9939609, in the FTO gene showed a much stronger association with all‐cause mortality than expected from its association with body mass index ( BMI ), body fat mass index ( FMI ) and waist circumference ( WC ). This finding implies that the SNP has strong pleiotropic effects on adiposity and adiposity‐independent pathological pathways that leads to increased mortality. To investigate this further, we conducted a meta‐analysis of similar data from 34 longitudinal studies including 169,551 adult C aucasians among whom 27,100 died during follow‐up. Linear regression showed that the minor allele of the FTO SNP was associated with greater BMI ( n = 169,551; 0.32 kg m −2 ; 95% CI 0.28–0.32, P &lt; 1 × 10 −32 ), WC ( n = 152,631; 0.76 cm; 0.68–0.84, P &lt; 1 × 10 −32 ) and FMI ( n = 48,192; 0.17 kg m −2 ; 0.13–0.22, P = 1.0 × 10 −13 ). C ox proportional hazard regression analyses for mortality showed that the hazards ratio ( HR ) for the minor allele of the FTO SNPs was 1.02 (1.00–1.04, P = 0.097), but the apparent excess risk was eliminated after adjustment for BMI and WC ( HR : 1.00; 0.98–1.03, P = 0.662) and for FMI ( HR : 1.00; 0.96–1.04, P = 0.932). In conclusion, this study does not support that the FTO SNP is associated with all‐cause mortality independently of the adiposity phenotypes.