Methods
Colocalization and Mendelian randomization analyses were performed.
Briefly, colocalization compares the proportionality of the genetic
associations for two traits within a given genetic locus, investigating
whether the data supports a model with a shared causal variant for both
traits3. In Mendelian randomization, genetic variants
that proxy the effect of varying the exposure are used to investigate
its effect on an outcome4. Further details are
provided in the Supplementary Methods.
Summary statistics data for the genetic associations of
single-nucleotide polymorphisms with each trait were obtained from
publicly available large-scale genome-wide association studies (GWAS)
performed on individuals of European ancestries. These data can be
obtained from the original studies, as detailed below. Genetic
associations with circulating GDF15 levels were based on 3,301 healthy
individuals5, genetic associations with BMI were
obtained from a GWAS meta-analysis of 806,834
individuals6, and genetic associations with type 2
diabetes liability were based on a GWAS meta-analysis of 74,124 cases
and 824,006 controls7. Relevant ethical approval and
participant consent were obtained by the original studies.