Fig. 1

Analysis pipeline and explanations for observed associations between single nucleotide polymorphisms (SNPs) and traits. a Five potential scenarios that could explain findings from the expression quantitative trait loci-wide association study (eQTLWAS): 1) The genetic variant influences the trait, mediated by the expression of a single gene at a locus. 2) The genetic variant influences the trait via multiple genes which are co-regulated with one another. 3) The genetic variant influences the trait via a single gene which is co-regulated with other non-causal genes. 4) The genetic variant that influences the trait is in linkage disequilibrium with another variant which is responsible for the changes in gene expression levels. 5) The genetic variant influences both gene expression and the trait outcome by two independent biological pathways (horizontal pleiotropy). b Flow diagram illustrating the analysis pipeline used to interrogate the causal pathway from SNP to trait. eQTLWAS was performed to uncover genetic variants associated with nearby gene expression and complex trait. Fine-mapping was implemented to identify potential causal variants. Mendelian randomization (MR) analyses were performed to interrogate scenarios 1, 2 and 3. Multiple-trait colocalization explored shared causal variants between traits (scenario 4). We were unable to investigate horizontal pleiotropy due to an insufficient number of instruments (scenario 5)