Table 2 Existing studies of pharmacodynamic-altering side effect susceptibility genes and overlapping DISLoDGED pathways*.

From: Pharmacogenomic and clinical data link non-pharmacokinetic metabolic dysregulation to drug side effect pathogenesis

1 Side effect	2 DISLoDGED Pathway (# metabolites in pathway)	3 PD gene	4 Nutrient overlap	5 Patho-physiology	6 Metabolic perturbation	7 In vivo drug perturbation	8 Supplement
Weight gain	Melatonin	MC4R	MC4R levels correlated with melatonin	Melatonin and MC4R energy regulators	Decreased melatonin tied to metabolic syndrome	Antipsychotics suppress melatonin synthesis	Melatonin
Parkinsonism	Poly-unsaturated fatty acids	ZNF202	ZNF202 lipid regulator	PUFAs linked to Lewy bodies	Altered lipid oxidation	RBC PUFAs altered	Essential fatty acids
Tardive Dyskinesia	Serotonin	5-HT receptors	Direct ligand	Dopaminergic neuron interaction	NA	5-Hydroxy-indoleacetate perturbation	Conflicting findings
Tardive Dyskinesia	Ascorbate	D3 receptors	Dopamine synthesis cofactor	Dopamine primary mediator	NA	Metabolite levels perturbed	Vitamin C, vitamin E
Myotoxicity	CoQ10	COQ2	CoQ10 synthesis	Mitochondrial function	Q10 deficiency associated w/ myopathy	Decreased under statin treatment	CoQ10 (conflicting)
Cardiac arrhythmia	Urea cycle	NOS1AP	Nitrogen regulation	NO affects cardiac function	Altered NO linked to arrhythmia	Various affect NO production	L-arginine
Cardiac arrhythmia	Pentose phosphate pathway	GPD1L, ZFHX3	Oxidative stress response	Oxidative stress affects cardiac function	H₂O₂ induces arrhythmia	Clomipramine induces via oxidative stress	Various antioxidants
Hearing loss	Ascorbate	COMT	Dopamine synthesis cofactor	Dopamine innervation in inner ear	Dopa synth. inhibition tied to hearing loss	Cisplatin inhibits dopamine	Vitamin C, dopamine
Hearing loss	Ascorbate, lipoate	Glutathione S-transferases	Oxidative stress response	ROS-induced cochlear cell death	SOD deficiency tied to hearing loss	Cisplatin induces via oxidative stress	Vitamin C, lipoate

Abbreviations: NA, not applicable; PUFA, poly-unsaturated fatty acids; RBC, red blood cell; ROS, reactive oxygen species; SOD, superoxide dismutase; 5-HT, serotonin.
^*Existing studies of pharmacodynamic-altering side effect susceptibility genes and overlapping DISLoDGED pathways. The two cases of tardive dyskinesia have ‘NA’ in the ‘Metabolic perturbation in disease’ row as tardive dyskinesia is not typically described as a disease outside of its occurrence as an adverse drug response, therefore there is no drug-independent case for comparison. See the Supplementary Note 1 for full discussion and references related to each case.

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Table 2 Existing studies of pharmacodynamic-altering side effect susceptibility genes and overlapping DISLoDGED pathways*.

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