Figure 1.

Directed acyclic graph of the effect of smoking on PD using genetic variants (SNPs) as proxies. (Adapted from Lawlor et al.²²). An SNP (S) is associated with the exposure, for example, smoking (E), and therefore the SNP (S) can be used as an instrument to determine the effect of smoking (E) on PD, which is the outcome of interest (O). An association between the smoking-risk-increasing SNP (S) and elevated risk of PD is consistent with a causal relationship between E and O if three assumptions are met: (1) The SNP (S) must be strongly associated with smoking (E); (2) The SNP (S) must be independent of any confounding factors (C) that may be influencing PD (O) and (3) The SNP (S)’s association with PD (O) is explained only via smoking (E). SNP, single nucleotide polymorphism.