Figure 2.

(A) Comparison of genomic analysis approaches illustrated on a DNA schematic, including 22 pairs of autosomal and sex chromosomes. Orange shaded regions indicate genetic materials used for analysis. (Left) GWAS analyses assess association of phenotype of interest with all sequenced SNPs, often hundreds of thousands, independently. Hence all chromosomes are shaded orange. (Right) On the other side of the technical spectrum, candidate gene approaches focus on a single polymorphism, often well motivated by prior biological data. In this example, the non-synonymous rs4680 SNP of the COMT gene is selected. (Middle) A pathway approach offers a compromise, where prior biological information is leveraged to define a set of genes, organized around a biological process. In this example, all genes whose products have an impact on dopaminergic neurotransmission are selected. (B) Dopamine metabolic pathway captures the biological process involved in neurotransmission, including dopamine synthesis (blue), dopamine signal transduction (orange), and dopamine transport and clearance (green). In principle, genes that regulate/act on these dopaminergic genes can also be included, although we do not include them here as they have broad functions in the nervous system.