Table 3:

Summary of 11 prior pediatric risperidone pharmacogenomic studies totaling 848 children.

Study	Genes and Variants	Outcomes	Number of Participants	Age of Participants	Results
Youngster, et al.21	CYP2D6 *2, *3, *4, *5, *6, *8, *9, *10, *11, *14, *15, *17, *18, *19, *20, *25, *26, *29, *30, *31, *35, *36, *37, *40, *41, *43, *52, and gene duplication	Weight gain and neurological events	40	3–18 years	AEs in 2/2 PMs, 9/35 IMs/NMs, and 0 UMs, but non significant association of PMs vs IMs/NMs (P=0.08) and UMs vs IMs/NMs (p=1.0); however, PMs had higher risperidone levels (p=0.03) and higher ratios of risperidone to metabolite (p=0.02) compared to IMs/NMs
Nussbaum, et al.22	CYP2D6 *4	Weight gain	81	9–20 years	IMs with more weight gain than NMs/RMs/UMs (p<0.001)*
Dos Santos-Júnior, et al.23	CYP2D6 * 10	Weight gain, hypertension, and metabolic abnormalities	120	8–20 years	Increased hypertension (p=0.039) and abdominal circumference (p=0.016) in PMs vs IMs/NMs/RMs/UMs
Grădinaru R, et al.24	CYP2D6 *3, *4, *5, *41	Prolactin and clinical adverse events	81	9–20 years	IMs with increased prolactin during treatment vs NMs (p<0.001)*
Correia, et al.25	CYP2D6 *3, *4, *5, *6, gene duplication	BMI, waist circumference, neurological events	45	3–21 years	UMs associated with BMI or waist circumference increase vs NMs (p=0.002)
Correia, et al.24	HTR2A rs6311	BMI, waist circumference, neurological events	45	3–21 years	Wild type with increased prolactin (p=0.006) vs non-wild type
Rafaniello, et al.7	CYP3A4 *22 CYP3A5*3	Liver enzymes and adverse events	64	Below 18 years	No association
Correia, et al.25	DRD3 rs6280	BMI, waist circumference, neurological events	45	3–21 years	No association
Rafaniello, et al.7	ABCB1 rs1045642 and rs2032582	Liver Enzymes, creatinine, and adverse events	64	Below 18 years	No association
Correia, et al.25	ABCB1 rs1128503 and rs1045642	BMI, waist circumference, neurological events	45	3–21 years	No association
Sukasem, et al.26	ABCB1 rs2032582 and rs1045642	Insulin resistance	89	3–20 years	No association
Dos Santos-Júnior, et al.23	HTR2C rs1414334, rs6318 and rs3813929	Weight gain and metabolic abnormalities	120	8–20 years	rs6318 heterozygotes with increased abdominal circumference in females compared to wild type/heterozygotes (p=0.035); rs3813929 heterozygotes with increased leptin compared to hemi/homozygotes (p=0.044)
Correia, et al.25	HTR2C rs6318, rs3813928, and rs3813929	BMI, waist circumference, neurological events	45	3–21 years	rs6318 wild type women/hemizygous men with lower prolactin increase than homo/ hemizygotes (p=0.006); rs6318 homozygous women and male hemizygotes with increased waist circumference (p<0.01) and BMI (p=0.037) compared to wild type
Hoekstra, et. Al19	HTR2C rs1414334 and rs3813929	BMI	32	5–16 years	rs3813929 homo/heterozygotes with reduced weight gain compared to wild type (p<0.001)
Del Castillo, et. al27	HTR2C rs3813929	BMI	45	7–17 years	No association
Almandil, et. al28	HTR2C rs1414334	BMI	144	2–17 years	No association
Rafaniello, et al.7	ABCG2 rs2231142	Liver Enzymes, creatinine, and adverse events	64	Below 18 years	Variant homozygotes with higher probability of nutrition and metabolism disorders (p=0.008) vs heterozygotes/ wild type*
Dos Santos-Júnior, et al.23	DRD2 rs6277 and rs1799978	Weight gain and metabolic abnormalities	120	8–20 years	rs1799978 heterozygotes with increased insulin resistance compared to wild type (p=0.010); Homozygotes of rs6277 with increased insulin resistance compared to wild type (p=0.053)
Calarge, et al.29	DRD2 rs6277, rs1800497, rs1799732, rs 1799978	Prolactin	107	7–17 years	rs1799978 hetero/homozygotes with increased prolactin elevation compared to wildtype in multivariable model (p=0.002); rs1800497 allele carriers with increased prolactin elevated compared to wild type (p=0.04)

^*Included other antipsychotics

PM-Poor metabolizers

IM-Intermediate metabolizers

NM-Normal metabolizers

RM-Rapid metabolizers

UM-Ultrarapid metabolizers