Table 1.
Mapping genetic risk from genome to syndrome using an intermediate phenotype approach
| Level of analysis | Observed variation | Example: Hutchison et al. [24••]a,b |
|---|---|---|
| Genome | Polymorphism | G →A SNP (rs6122429) |
| Intra-/Intercellular milieu | Transcription/biochemical | GG = ↑ binding |
| Physiologic system (body/brain)b | System/network | GG = ↑ a4* NAChR/DA activity (putative) |
| Proximal intermediate phenotype | Motivational | GG = ↑ smoking reward |
| Clinical | Presence/severity | GG = ↑ nicotine dependence/smoking |
a
A guanine (G) to adenine (A) substitution at position 4490 in the CHRNA4 gene is a single nucleotide polymorphism (SNP) for which homozygous G genotype was found to be associated with increased binding, subjective smoking reward, and nicotine dependence.
b
A level of analysis not examined in the study was the physiologic system, where the observed transcriptional variation putatively alters cholinergic and/or dopaminergic activity.