Gene Name	Entrez ID	Drug Name	Chembl ID	Interaction Types	Sources	publications
COMT	1312	ENTACAPONE	CHEMBL953	inhibitor	TdgClinicalTrial, GuideToPharmacologyInteractions, ChemblInteractions, TEND, DrugBank, TTD	11752352, 11939936, 9808337, 10439935, 11873938, 10882160, 10981253, 12538800, 12876237, 11440283
COMT	1312	BUPROPION	CHEMBL894		PharmGKB
COMT	1312	METHYLDOPA	CHEMBL459		PharmGKB
COMT	1312	S-ADENOSYL-L-METHIONINE	CHEMBL24991	cofactor	DrugBank	18486144, 20196537
COMT	1312	TOLCAPONE	CHEMBL1324	inhibitor	GuideToPharmacologyInteractions, TdgClinicalTrial, TEND, DrugBank, ChemblInteractions, TTD	9917075, 12538800, 17063156, 11752352, 9808337, 15697329, 11873938, 10882160, 20502133, 19503773, 18046910
COMT	1312	3,5-DINITROCATECHOL (OR-486)	CHEMBL168276		DrugBank	17139284, 17016423, 10592235
COMT	1312	CHEMBL1233867	CHEMBL1233867		DrugBank	10592235
COMT	1312	RISPERIDONE	CHEMBL85		PharmGKB
COMT	1312	CHEMBL387347	CHEMBL387347		DrugBank	10592235
COMT	1312	CARBOQUONE	CHEMBL443014		PharmGKB
COMT	1312	LEVODOPA	CHEMBL1009		PharmGKB
COMT	1312	D-PROLINE	CHEMBL80257	inhibitor	GuideToPharmacologyInteractions
COMT	1312	NIALAMIDE	CHEMBL1256841		DrugBank	1170911
COMT	1312	2-METHOXYESTRADIOL	CHEMBL299613		DrugBank	1170911

Gene Name	Variant	Alleles	Chemical	Phenotype Category	Significance	Notes	Sentence	Publications	Annotation ID
COMT	rs4680	A	buprenorphine	dosage	no		Allele A is not associated with dose of buprenorphine, dihydrocodeine, fentanyl, hydromorphone, methadone, oxycodone, piritramide, tilidine or tramadol in people with Pain as compared to allele G.	19514130	1183682029
COMT	rs4680	GG	opioids	dosage	yes	G allele is referred to as the 'Val' allele in the paper. Patients with the GG genotype had significantly increased opioid consumption, as measured in morphine equivalents, compared to AA or AG patients.	Genotype GG is associated with increased dose of opioids in women with Breast Neoplasms and Pain, Postoperative as compared to genotypes AA + AG.	27729204	1451221008
COMT	rs4680	AA + AG	opioids	efficacy	yes	Patients with the AA or AG genotypes reached the lowest pain intensity faster than those with the GG genotype.	Genotypes AA + AG are associated with increased response to opioids in children as compared to genotype GG.	30704436	1450933135
COMT	rs4680	AA + AG	methylphenidate	efficacy	yes	Positive response defined as Clinical Global Impression-Improvement (CGI-I) rating of 'much improved' or 'very much improved', and decrease in Aberrant Behavior Checklist-Hyperactivity subscale of >25% from baseline. This result was not significant when considering correction for multiple testing (p<0.002).	Genotypes AA + AG is associated with increased response to methylphenidate in children with Autism Spectrum Disorder as compared to genotype GG.	23856854	1184510536
COMT	rs4680	AA + AG	glucose	toxicity	yes	After adjusting for covariates, children treated with second-generation antipsychotics who carried the A allele ("Met allele") had higher fasting glucose concentrations as compared to those homozygous for the G allele ("Val allele").	Genotypes AA + AG is associated with increased concentrations of glucose in children as compared to genotype GG.	25048416	1444934745
COMT	rs4680	GG	methylphenidate	efficacy	yes	The A allele and G allele are reported in the paper as the Val allele and Met allele respectively.	Genotype GG is associated with increased response to methylphenidate in children with Attention Deficit Disorder with Hyperactivity as compared to genotypes AA + AG.	29230023	1450180302
COMT	rs4680	GG	morphine	efficacy	yes	Infants with the GG genotype took longer to achieve a pain-free ALPS-Neo score than infants with the AA or AG genotypes. The paper refers to these alleles as Val and Met, where the G allele = Val and the A allele = Met.	Genotype GG is associated with decreased response to morphine in infants with Pain as compared to genotypes AA + AG.	27027462	1450373824
COMT	rs4680	AA	remifentanil	efficacy	yes	Infants with the AA genotype were quicker to achieve a pain-free ALPS-Neo score than infants with the AG or GG genotypes. The paper refers to these alleles as Val and Met, where the G allele = Val and the A allele = Met.	Genotype AA is associated with increased response to remifentanil in infants with Pain as compared to genotypes AG + GG.	27027462	1450373834
COMT	rs4680	G	methylphenidate	efficacy	yes	G allele (Val) showed a significant association with good methylphenidate response P = 0.009. The G/G genotype was twice as frequent in the responder group compared to the non-responders P = 0.034. No genotyping information included in the article.	Allele G is associated with increased clearance of methylphenidate in children with Attention Deficit Disorder with Hyperactivity as compared to allele A.	18214865	1450374923
COMT	rs4680	GG	methylphenidate	efficacy	yes	Symptom severity scores of all three genotype groups decreased following methylphenidate administration (P< 0.001), however G/G homozygote children had significantly less severe symptoms than those with A/A genotype after treatment (P = 0.015). Note: article also states: Methylphenidate also significantly decreased the CGI-S scores but this reduction was not modified by COMT genotypes.	Genotype GG is associated with increased response to methylphenidate in children with Attention Deficit Disorder with Hyperactivity as compared to genotype AA.	18214865	1450374932
COMT	rs4680	GG	methylphenidate	efficacy	not stated	62.5% (40/64) of the patients who showed a good response to treatment with MPH had the G/G genotype, 41.7% (25/60) and 11.7% (7/60) of the patients who showed a poor response to treatment with MPH according to ARS assessed by their teachers had the G/A and A/A genotype P = 0.035. Significant difference for Met/Met genotype frequency between treatment responder and nonresponder groups (P = 0.029).	Genotype GG is associated with increased response to methylphenidate in children with Attention Deficit Disorder with Hyperactivity as compared to genotypes AA + AG.	18703939	1450374939
COMT	rs4680	G	methylphenidate	efficacy	no	Scales used to assess response: ADHD-RS-IV, SWAN, and Permanent product Measure of Performance (PERMP). A trend of effect was detected for the COMT variant. significance = p<0.025	Allele G is not associated with response to methylphenidate in children with Attention Deficit Disorder with Hyperactivity as compared to allele A.	19858760	1450376375
COMT	rs4680	G	methylphenidate	efficacy	no	Clinical Global Impression-Severity (CGI-S) scale and the Children’s Global Assessment Scale (CGAS).	Allele G is not associated with response to methylphenidate in children with Attention Deficit Disorder with Hyperactivity as compared to allele A.	28871191	1450376626
COMT	rs4680	AA + AG	methylphenidate	efficacy	not stated	The outcome measure was the parent-rated oppositional subscale of the Swanson, Nolan and Pelham Scale-Version IV (SNAP-IV). Effect of the presence of the Met allele on mean reductions in SNAP-IV oppositional scores from baseline in a mixed-effects model (n = 112). Presence of the Met allele: p = 0.019.	Genotypes AA + AG are associated with increased response to methylphenidate in children with Attention Deficit Disorder with Hyperactivity as compared to genotype GG.	21550019	1450376659
COMT	rs4680	G	methylphenidate	efficacy	no	No significant difference in MPH effect/adverse effects was observed in association with the COMT genotype in the ADHD group. To evaluate symptom improvement, the ADHD-RS total score transition after 3 months of MPH treatment was chosen.	Allele G is not associated with response to methylphenidate in children with Attention Deficit Disorder with Hyperactivity as compared to allele A.	24035255	1450376668
COMT	rs4680	G	methylphenidate	efficacy	no	Vanderbilt ADHD Parent Rating Scales and Vanderbilt ADHD Teacher Rating Scales - hyperactive-impulsive domain score was derived by totaling scores from the nine hyperactive-impulsive symptoms.	Allele G is not associated with response to methylphenidate in children with Attention Deficit Disorder with Hyperactivity as compared to allele A.	22024001	1450376686
COMT	rs4680	GG	methylphenidate	efficacy	not stated	Parents of the children completed the parent version of the ADHD Rating Scale-IV (ADHD-RS), and certified child and adolescent psychiatrists administered the Clinical Global Impressions-Severity (CGI-I) Scale. The study found a significant association between the Val/Val genotype and a good response, in terms of hyperactive-impulsive (p = 0.044) but not inattentive (p = 0.474) scores on the ADHD-RS; however, no significant association was found between the COMT (Val158-Met) polymorphism genotype and the relative frequency of CGI-I 1 or 2 scores. An association was seen between the Val/ Val genotype and a good response in terms of response-time variability (p = 0.028), but not omission errors, commission errors nor response-time scores on the CPT.	Genotype GG is associated with increased response to methylphenidate in children with Attention Deficit Disorder with Hyperactivity as compared to genotypes AA + AG.	24763183	1450376695
COMT	rs4680	G	methylphenidate	efficacy	no	Patients underwent the same naturalistic assessment procedure to evaluate the treatment response, which included the reapplication of the CPRS, CTRS, CGI-S, GAS, CPT and TMT A and B. Treatment responders were defined as follows: patients registering 2 points or greater improvement on the CGI-S and a total GAS score of 60 points or greater (out of 108 subjects 66.6% responded to the treatment, while 33.3% did not). No association for distribution of genotypes according to treatment response.	Allele G is not associated with response to methylphenidate in children with Attention Deficit Disorder with Hyperactivity as compared to allele A.	27482244	1450376712
COMT	rs4680	G	methylphenidate	efficacy	no	No significant genotype by treatment interaction was observed (p=0.4), suggesting that COMT genotype does not modulate therapeutic response, at least at the dose of MPH tested (0.5¿mg/kg). Restricted Academic Situation Scale (RASS) was used.	Allele G is not associated with response to methylphenidate in children with Attention Deficit Disorder with Hyperactivity as compared to allele A.	18580877	1450376738
COMT	rs4680	AG + GG	bupropion	efficacy	yes	Relationship is reported as beneficial for Met/Val or Val/Val compared to Met/Met. The rs number is listed but not which base corresponds to the protein change: Met = rs4680A and Val = rs4680G.	Genotypes AG + GG is associated with increased response to bupropion in people with Depressive Disorder, Major as compared to genotype AA.	32459054	1451270680
COMT	rs4680	A	morphine	efficacy	yes		Allele A is associated with increased response to morphine in people with Low Back Pain as compared to allele G.	23773341	1449173508
COMT	rs4680	AG + GG	morphine	efficacy	yes		Genotypes AG + GG are associated with increased dose of morphine as compared to genotype AA.	17156920	731493498
COMT	rs4680	AG + GG	venlafaxine	efficacy	no	Hamilton Depression Rating Scale (HDRS) scores improved over time in each genotype (GG, AG and AA P=0.001; P<0.001 and P<0.001) Hamilton Depression Rating Scale (HDRS) but in mixed models, responder status was not associated with the either allele. The GG and AG genotype improved HDRS scores after three and six months of treatment and was not seen in the AA genotype.	Genotypes AG + GG is not associated with response to venlafaxine in people with Depressive Disorder, Major as compared to genotype AA.	28627776	1448639101
COMT	rs4680	A	morphine	dosage	no		Allele A is not associated with dose of morphine in people with Pain, Postoperative as compared to allele G.	29474345	1449173347
COMT	rs740603	A	morphine	"dosage","efficacy"	yes	This was for alleviation of pain from cancer. The association was as part of a haplotype consisting of 11 rsIDs (the other rsIDs are rs2075507,rs7287550, rs5746849, rs737866, rs6269, rs2239393, rs4818, rs4680, rs174699, rs165728). The haplotype was associated with a dose reduction factor of 0.71 . Authors state that because the SNPs are linked, a strict Bonferroni correction is too conservative; however, that is what has been done here for p value. Also noted was that the carriers of haplotype 1 have had the cancer diagnosis longer than have carriers of other haplotypes, and so the true difference in morphine requirements may be even greater than observed here.	Allele A is associated with decreased dose of morphine in people with Neoplasms as compared to allele G.	19094200	981862185
COMT	rs9606186	C	risperidone	efficacy	yes	When combined with the C allele in rs2020917 and the C allele in rs933271. Patients with the haplotype C-C-C across these three SNPs have poorer response to risperidone. "Responders" were classified as patients who showed a reduction of 40% or more in Brief Psychiatric Rating Scale (BPRS) scores after 8 weeks of risperidone monotherapy. All other patients were considered "nonresponders".	Allele C is associated with decreased response to risperidone in people with Schizophrenia.	22935916	982015818
COMT	rs4680	GG	antidepressants	efficacy	no		Genotype GG is not associated with response to antidepressants in people with Depressive Disorder, Major as compared to genotypes AA + AG.	23733030	982028756
COMT	rs4680	A	methylphenidate	efficacy	no		Allele A is not associated with response to methylphenidate in people with Attention Deficit Disorder with Hyperactivity as compared to allele G.	23131881	981478829
COMT	rs165599	AA + AG	bupropion	efficacy	yes	GG smokers quit more readily on placebo. On bupropion, A carriers had 19% abstinence on placebo and 33% abstinence on bupropion, while GG smokers had 38% abstinence on placebo and 22% abstinence on bupropion. Also, the haplotype with rs737865 may be important. G-G haplotype (for rs737865 and rs165599) smokers of European-American ethnicity may not benefit from bupropion, while the smokers of European-American origin with an A allele at rs165599 have a substantial probability of benefit.	Genotypes AA + AG are associated with increased response to bupropion in smokers as compared to genotype GG.	16876132	981419300
COMT	rs737865	AA	bupropion	efficacy	yes	Authors caution inadequate power for this to be a strong conclusion.	Genotype AA is associated with decreased response to bupropion in smokers as compared to genotypes AG + GG.	16876132	981419313
COMT	rs5746849	A	morphine	"dosage","efficacy"	yes	This was for alleviation of pain from cancer. The association was as part of a haplotype consisting of 11 rsIDs (the other rsIDs are rs2075507,rs7287550, rs737866, rs740603, rs6269, rs2239393, rs4818, rs4680, rs174699, rs165728). The haplotype was associated with a dose reduction factor of 0.71 . Authors state that because the SNPs are linked, a strict Bonferroni correction is too conservative; however, that is what has been done here for p value. Also noted was that the carriers of haplotype 1 have had the cancer diagnosis longer than have carriers of other haplotypes, and so the true difference in morphine requirements may be even greater than observed here.	Allele A is associated with decreased dose of morphine in people with Neoplasms as compared to allele G.	19094200	981862176
COMT	rs933271	C	risperidone	efficacy	yes	When combined with the C allele in rs9606186 and the C allele in rs2020917. Patients with the haplotype C-C-C across these three SNPs have poorer response to risperidone. "Responders" were classified as patients who showed a reduction of 40% or more in Brief Psychiatric Rating Scale (BPRS) scores after 8 weeks of risperidone monotherapy. All other patients were considered "nonresponders".	Allele C is associated with decreased response to risperidone in people with Schizophrenia.	22935916	982015810
COMT	rs4680	G	antipsychotics	efficacy	no		Allele G is not associated with response to antipsychotics in people with Schizophrenia as compared to allele A.	19290789	982025810
COMT	rs4633	T	antipsychotics	efficacy	no		Allele T is not associated with response to antipsychotics in people with Schizophrenia as compared to allele C.	19290789	982025799
COMT	rs2020917	C	risperidone	efficacy	yes	When combined with the C allele in rs9606186 and the C allele in rs933271. Patients with the haplotype C-C-C across these three SNPs have poorer response to risperidone. "Responders" were classified as patients who showed a reduction of 40% or more in Brief Psychiatric Rating Scale (BPRS) scores after 8 weeks of risperidone monotherapy. All other patients were considered "nonresponders".	Allele C is associated with decreased response to risperidone in people with Schizophrenia.	22935916	982015800
COMT	rs4680	G	lithium	efficacy	not stated	This is from a review article which does not give all the details. It says that no association was found between the SNP and lithium response, but it does not state exactly how the alleles were compared.	Allele G is not associated with response to lithium in people with Bipolar Disorder as compared to allele A.	21047205	699639182
COMT	rs174696	C	morphine	"dosage","efficacy"	no	Haplotype of the six COMT variants studied in the paper was also not significantly associated with morphine dose requirements. A stepwise backward linear regression model of age, rs9340799, rs1799971, rs4986936, rs1319339, rs174696, rs677830, rs4680, rs4818, and rs540825 was found to explain 10.7% of variance in morphine dose requirements in the study cohort (p=0.001)	Allele C is not associated with dose of morphine in people with Pain, Postoperative as compared to allele T.	26902643	1449295951
COMT	rs4680	AA + AG	venlafaxine	efficacy	yes	The rs4680 A allele was associated with increased response to venlafaxine as measured on the Clinical Global Impression of Improvement (CGI-I) scale, as compared to GG homozygotes. No significant association was seen for remission on this same scale. Patients were treated with venlafaxine for 6 months.	Genotypes AA + AG are associated with increased response to venlafaxine in people with Anxiety Disorders as compared to genotype GG.	22417933	981848236
COMT	rs5993883	T	quetiapine	efficacy	yes	This association was significant after Bonferroni correction. The T allele was frequently observed in poor responders to quetiapine. Patients were classified as good responders if they had a reduction of Positive and Negative Syndrome Scale (PANSS) score of >=50% and poor responders if they had a reduction of PANSS score of <50%.	Allele T is associated with decreased response to quetiapine in people with Schizophrenia as compared to allele G.	26282453	1448423725
COMT	rs6269	A	quetiapine	efficacy	yes	This association was significant after Bonferroni correction. The A allele was frequently observed in poor responders quetiapine. Patients were classified as good responders if they had a reduction of Positive and Negative Syndrome Scale (PANSS) score of >=50% and poor responders if they had a reduction of PANSS score of <50%.	Allele A is associated with decreased response to quetiapine in people with Schizophrenia as compared to allele G.	26282453	1448423713
COMT	rs4818	C	quetiapine	efficacy	yes	This association was significant after Bonferroni correction. The C allele was frequently observed in poor responders to quetiapine. Patients were classified as good responders if they had a reduction of Positive and Negative Syndrome Scale (PANSS) score of >=50% and poor responders if they had a reduction of PANSS score of <50%.	Allele C is associated with decreased response to quetiapine in people with Schizophrenia as compared to allele G.	26282453	1448423731
COMT	rs4680	A	morphine	"dosage","efficacy"	yes	This was for alleviation of pain from cancer. The association was as part of a haplotype consisting of 11 rsIDs (the other rsIDs are rs2075507,rs7287550, rs5746849, rs737866, rs6269, rs2239393, rs4818, rs740603, rs174699, rs165728). The haplotype was associated with a dose reduction factor of 0.71 . Authors state that because the SNPs are linked, a strict Bonferroni correction is too conservative; however, that is what has been done here for p value. Also noted was that the carriers of haplotype 1 have had the cancer diagnosis longer than have carriers of other haplotypes, and so the true difference in morphine requirements may be even greater than observed here.	Allele A is associated with decreased dose of morphine in people with Neoplasms as compared to allele G.	19094200	981862203
COMT	rs4680	A	risperidone	efficacy	no	No significant association was seen between any rs4680 allele or genotype and the number of "responders". "Responders" were classified as patients who showed a reduction of 40% or more in Brief Psychiatric Rating Scale (BPRS) scores after 8 weeks of risperidone monotherapy. All other patients were considered "nonresponders".	Allele A is not associated with response to risperidone in people with Schizophrenia.	22935916	981859133
COMT	rs4680	GG	venlafaxine	efficacy	yes	Response was reported as week 8 change from baseline HAM-D-17 as compared to placebo per genotype. For GG carriers venlafaxine treatment response appeared larger ( - 5.9 points, p-value 0.0013 versus placebo, unadjusted for multiplicity), when compared to AG and carriers. But the confidence intervals are overlapping.	Genotype GG is associated with increased response to venlafaxine in people with Depressive Disorder, Major as compared to genotypes AA + AG.	23706899	982023623
COMT	rs4680	GG	nicotine	efficacy	yes	Patients with the GG genotype who were treated with sublingual nicotine as treatment for nicotine dependence had a greater likelihood of smoking abstinence after 12 weeks of treatment, as compared to A allele carriers. After 8 weeks of treatment with sublingual nicotine, patients stopped taking the drug. Abstinence was defined as neither a cigarette nor any other form of nicotine for at least 7 continuous days between when sublingual nicotine treatment ceased (week 8) and final follow-up (week 12).	Genotype GG is associated with increased response to nicotine in people with Tobacco Use Disorder as compared to genotypes AA + AG.	22695756	982047201
COMT	rs4680	GG	opioids	dosage	yes	Patients with the combined OPRM1 118AG/GG (rs1799971) and COMT 472GG (rs4680) genotype required 50% higher dose increase for sufficient analgesia	Genotype GG is associated with increased dose of opioids in people with Neoplasms and Pain as compared to genotypes AA + AG.	28745577	1448818544
COMT	rs4680	GG	clozapine	efficacy	yes	Patients with the GG genotype (described as Val/Val in the paper) had a greater improvement on the Positive and Negative Symptoms Scale (PANSS), Negative Symptoms Subscale, as compared to those with the AA or AG genotypes (described as Met carriers). PANSS score was measured at baseline and then after 12 weeks of treatment.	Genotype GG is associated with increased response to clozapine in people with Schizophrenia as compared to genotypes AA + AG.	25560469	1444699493
COMT	rs4680	AA + AG	antipsychotics	efficacy	no	Patients' psychopathological symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Drugs prescribed were clozapine (58 patients), risperidone (28 patients), aripiprazole (25 patients), quetiapine (18 patients), olanzapine (12 patients), paliperidone (3 patients), ziprasidone (1 patient), fluphenazine (21 patients), zuclopenthixol (19 patients), amisulpride (13 patients), flupentixol (9 patients), promazine (7 patients), and haloperidol (3 patients).	Genotypes AA + AG are not associated with response to antipsychotics in people with Schizophrenia as compared to genotype GG.	27287786	1448258581
COMT	rs4680	A	fentanyl	dosage	no	Despite the lack of significance between this individual variant and fentanyl consumption, haplotypes of rs6269, rs4633, rs4818 and rs4680 were significantly associated with fentanyl dose. Please see the paper for further details.	Allele A is not associated with dose of fentanyl in people with Pain, Postoperative as compared to allele G.	25532715	1449716707
COMT	rs4680	G	morphine	"dosage","efficacy"	no	Linearity test showed a relationship between the number of G alleles and increasing morphine dose (i.e. AA < AG < GG). Haplotype of the six COMT variants studied in the paper was also not significantly associated with morphine dose requirements. A stepwise backward linear regression model of age, rs9340799, rs1799971, rs4986936, rs1319339, rs174696, rs677830, rs4680, rs4818, and rs540825 was found to explain 10.7% of variance in morphine dose requirements in the study cohort (p=0.001)	Allele G is not associated with dose of morphine in people with Pain, Postoperative as compared to allele A.	26902643	1449295921
COMT	rs4680	G	methylphenidate	efficacy	no		Allele G is not associated with response to methylphenidate in children with Attention Deficit Disorder with Hyperactivity as compared to allele A.	22149470	1450374950
COMT	rs4680	AA + AG	morphine	efficacy	yes	Infants with the AA or AG genotypes were quicker to achieve a pain-free ALPS-Neo score than infants with the GG genotype. The paper refers to these alleles as Val and Met, where the G allele = Val and the A allele = Met.	Genotypes AA + AG are associated with increased response to morphine or remifentanil in infants with Pain as compared to genotype GG.	27027462	1450373815
COMT	rs4818	C	morphine	"dosage","efficacy"	yes	This was for alleviation of pain from cancer. The association was as part of a haplotype consisting of 11 rsIDs (the other rsIDs are rs2075507,rs7287550, rs5746849, rs737866, rs6269, rs2239393, rs740603, rs4680, rs174699, rs165728). The haplotype was associated with a dose reduction factor of 0.71 . Authors state that because the SNPs are linked, a strict Bonferroni correction is too conservative; however, that is what has been done here for p value. Also noted was that the carriers of haplotype 1 have had the cancer diagnosis longer than have carriers of other haplotypes, and so the true difference in morphine requirements may be even greater than observed here. Since this is a G/C SNP, there is ambiguity regarding which is the associated allele. C is reported to be part of the haplotype associated with decreased dose, and this gene is on the positive chromosomal strand.	Allele C is associated with decreased dose of morphine in people with Neoplasms as compared to allele G.	19094200	981862218
COMT	rs4680	AA	morphine	"dosage","efficacy"	yes	Patients with the AA genotype required lower morphine doses than patients with the AG and GG genotypes. Patients with the AG genotype also required lower morphine doses than patients with the GG genotype.	Genotype AA is associated with decreased dose of morphine in people with Pain, Postoperative as compared to genotypes AG + GG.	23686330	1449295811
COMT	rs165722	C	opioids	dosage	no	Variant had no significant association with opioid dose in either the development sample or the validation sample.	Allele C is not associated with dose of opioids in people with Pain as compared to allele T.	21398039	1449715082
COMT	rs5993882	G	opioids	dosage	no	Variant had no significant association with opioid dose in either the development sample or the validation sample.	Allele G is not associated with dose of opioids in people with Pain as compared to allele T.	21398039	1449715075
COMT	rs165599	G	risperidone	efficacy	yes		Allele G is associated with increased response to risperidone in people with Schizophrenia.	19451915	699638917
COMT	rs4633	C	morphine	"dosage","efficacy"	no	Haplotype of the six COMT variants studied in the paper was also not significantly associated with morphine dose requirements.	Allele C is not associated with dose of morphine in people with Pain, Postoperative as compared to allele T.	26902643	1449295933
COMT	rs4818	G	morphine	"dosage","efficacy"	no	Haplotype of the six COMT variants studied in the paper was also not significantly associated with morphine dose requirements. A stepwise backward linear regression model of age, rs9340799, rs1799971, rs4986936, rs1319339, rs174696, rs677830, rs4680, rs4818, and rs540825 was found to explain 10.7% of variance in morphine dose requirements in the study cohort (p=0.001)	Allele G is not associated with dose of morphine in people with Pain, Postoperative as compared to allele C.	26902643	1449295939
COMT	rs4633	C	risperidone	efficacy	no	No significant association was seen between any rs4633 allele or genotype and the number of "responders". "Responders" were classified as patients who showed a reduction of 40% or more in Brief Psychiatric Rating Scale (BPRS) scores after 8 weeks of risperidone monotherapy. All other patients were considered "nonresponders".	Allele C is not associated with response to risperidone in people with Schizophrenia.	22935916	981859157
COMT	rs4680	AA	fentanyl	efficacy	no	Patients with the AA genotype had a 10% analgesia success rate compared to 22% in the AG and GG groups. However, this association was not statistically significant.	Genotype AA is associated with decreased response to fentanyl in women with as compared to genotypes AG + GG.	23302985	1449715221
COMT	rs4680	GG	fluvoxamine	efficacy	yes	The outcome was inversely proportional to the enzyme activity: better effects in Met-carriers (A-allele), worse effects in Val/Val homozygotes (G-allele). The effect became significant at the fourth week of treatment, and influence final response rates. Fluvoxamine plasma levels had marginal effects on outcome. Only abstract of the article available and no p-value was reported in the abstract.	Genotype GG is associated with decreased response to fluvoxamine in people with Depressive Disorder, Major as compared to allele A.	20619611	827816713
COMT	rs4680	GG	modafinil	efficacy	yes	Hispanic subjects with the GG genotype had significantly higher Treatment Effectiveness Scores when treated with modafinil compared to placebo. This significant association was not seen when comparing modafinil treatment against placebo in subject with the AA or AG genotypes.	Genotype GG is associated with increased response to modafinil in people with methamphetamine dependence as compared to genotypes AA + AG.	22217949	1450813963
COMT	rs9606186	C	risperidone	efficacy	no	Please note that alleles have been complemented to the positive strand.	Allele C is not associated with response to risperidone in people with Schizophrenia as compared to allele G.	28696411	1450928312
COMT	rs4680	AG	opioids	dosage	yes	Patients with the AG genotype had reduced consumption of opioids compared to those with the GG genotype.	Genotype AG is associated with decreased dose of opioids in children as compared to genotype GG.	30704436	1450933130
COMT	rs9606186	GG	risperidone	efficacy	yes	The GG genotype group had a higher percentage of "responders" compared to the CG and CC genotype groups. "Responders" were classified as patients who showed a reduction of 40% or more in Brief Psychiatric Rating Scale (BPRS) scores after 8 weeks of risperidone monotherapy. All other patients were considered "nonresponders". Significant results were seen for the entire study population and the male subgroup (n = 45). No significant results were seen for the female subgroup (n = 85).	Genotype GG is associated with increased response to risperidone in people with Schizophrenia as compared to genotypes CC + CG.	22935916	981859123
COMT	rs737865	G	oxycodone	efficacy	no	No association between this variant and analgesic response to oxycodone, as assessed by cold pressor test, subjective effects of oxycodone. Please note that alleles have been complemented to the positive strand.	Allele G is not associated with response to oxycodone as compared to allele A.	31493434	1451121689
COMT	rs4680	AA + AG	oxycodone	efficacy	yes	Subjects with the AA or AG genotypes had an increased subjective 'Stimulated' response to oxycodone than subjects with the GG genotype.	Genotypes AA + AG are associated with increased response to oxycodone as compared to genotype GG.	31493434	1451121600
COMT	rs165599	A	oxycodone	efficacy	no	No association between this variant and analgesic response to oxycodone, as assessed by cold pressor test, subjective effects of oxycodone.	Allele A is not associated with response to oxycodone as compared to allele G.	31493434	1451121685
COMT	rs4680	A	oxycodone	efficacy	no	No association between this variant and analgesic response to oxycodone, as assessed by cold pressor test.	Allele A is not associated with response to oxycodone as compared to allele G.	31493434	1451121640
COMT	rs4680	G	morphine	dosage	no	The setting was for palliative care of cancer patients.	Allele G is not associated with dose of morphine in people with Neoplasms as compared to allele A.	28346387	1448612967
COMT	rs4680	GG	fluoxetine	"dosage","efficacy"	no	However, authors note that GG subjects were responders "slightly more" than AG or AA. It was also noted that there was no placebo group in this trial. The association tested was with response at 4 weeks.	Genotype GG is not associated with response to fluoxetine in people with Depressive Disorder, Major as compared to genotypes AA + AG.	20584552	981502189
COMT	rs6269	A	morphine	"dosage","efficacy"	yes	This was for alleviation of pain from cancer. The association was as part of a haplotype consisting of 11 rsIDs (the other rsIDs are rs2075507,rs7287550, rs5746849, rs737866, rs6269, rs740603, rs4818, rs4680, rs174699, rs165728). The haplotype was associated with a dose reduction factor of 0.71 . Authors state that because the SNPs are linked, a strict Bonferroni correction is too conservative; however, that is what has been done here for p value. Also noted was that the carriers of haplotype 1 have had the cancer diagnosis longer than have carriers of other haplotypes, and so the true difference in morphine requirements may be even greater than observed here.	Allele A is associated with decreased dose of morphine in people with Neoplasms as compared to allele G.	19094200	981862194
COMT	rs737866	T	morphine	"dosage","efficacy"	yes	This was for alleviation of pain from cancer. The association was as part of a haplotype consisting of 11 rsIDs (the other rsIDs are rs2075507,rs7287550, rs5746849, rs740603, rs6269, rs2239393, rs4818, rs4680, rs174699, rs165728). The haplotype was associated with a dose reduction factor of 0.71 . Authors state that because the SNPs are linked, a strict Bonferroni correction is too conservative; however, that is what has been done here for p value. Also noted was that the carriers of haplotype 1 have had the cancer diagnosis longer than have carriers of other haplotypes, and so the true difference in morphine requirements may be even greater than observed here.	Allele T is associated with decreased dose of morphine in people with Neoplasms as compared to allele C.	19094200	981862160
COMT	rs2239393	A	morphine	"dosage","efficacy"	yes	This was for alleviation of pain from cancer. The association was as part of a haplotype consisting of 11 rsIDs (the other rsIDs are rs2075507,rs7287550, rs5746849, rs737866, rs6269, rs740603, rs4818, rs4680, rs174699, rs165728). The haplotype was associated with a dose reduction factor of 0.71 . Authors state that because the SNPs are linked, a strict Bonferroni correction is too conservative; however, that is what has been done here for p value. Also noted was that the carriers of haplotype 1 have had the cancer diagnosis longer than have carriers of other haplotypes, and so the true difference in morphine requirements may be even greater than observed here.	Allele A is associated with decreased dose of morphine in people with Neoplasms as compared to allele G.	19094200	981862234
COMT	rs4680	A	paroxetine	efficacy	yes	AA > AG > GG for response. A = Met allele; G = Val. The effect became significant at week 3 of treatment.	Allele A is associated with increased response to paroxetine in people with Depressive Disorder, Major as compared to allele G.	18989660	981954851
COMT	rs2075507	G	morphine	"dosage","efficacy"	yes	This was for alleviation of pain from cancer. The association was as part of a haplotype consisting of 11 rsIDs (the other rsIDs are rs737866,rs7287550, rs5746849, rs740603, rs6269, rs2239393, rs4818, rs4680, rs174699, rs165728). The haplotype was associated with a dose reduction factor of 0.71 . Authors state that because the SNPs are linked, a strict Bonferroni correction is too conservative; however, that is what has been done here for p value. Also noted was that the carriers of haplotype 1 have had the cancer diagnosis longer than have carriers of other haplotypes, and so the true difference in morphine requirements may be even greater than observed here.	Allele G is associated with decreased dose of morphine in people with Neoplasms as compared to allele A.	19094200	981862151
COMT	rs4680	GG	venlafaxine	efficacy	no	No association was seen between genotype and response or remission on the Hamilton Anxiety Scale (HAM-A). Patients were treated with venlafaxine for 6 months.	Genotype GG is not associated with response to venlafaxine in people with Anxiety Disorders as compared to genotypes AA + AG.	22417933	981848218
COMT	rs4680	GG	entacapone	efficacy	yes		Genotype GG is associated with increased response to entacapone in people with Parkinson Disease as compared to genotype AA.	21280081	982025681
COMT	rs4646312	C	opioids	dosage	no	Variant was significantly associated with opioid dose in the development sample, but lost significance in the validation sample.	Allele C is not associated with dose of opioids in people with Pain as compared to allele T.	21398039	1449714123
COMT	rs4680	A	escitalopram	efficacy	no		Allele A is not associated with response to escitalopram in people with Depression as compared to allele G.	31721892	1451148582
COMT	rs4680	A	methadone	efficacy	no	No significant difference in allele or genotype frequencies between responders and non-responders. Response was defined as "an absence of positive urine analysis, or at most, a one-time positive urine analysis for opioids during a 6-month follow-up period; nonconsumption of heroin or other types of opioid drugs according to participant self-reports; an absence of withdrawal symptoms; and a stable and regular attendance in the MMT therapeutic program". Note that the use of high-dose methadone was significantly lower in the non-responder group than in the responder group (p=0.01). This SNP was in high linkage disequilibirum with rs933271 and rs737866.	Allele A is not associated with response to methadone in people with Opioid-Related Disorders as compared to allele G.	32407152	1451148020
COMT	rs737866	C	methadone	efficacy	no	No significant difference in allele or genotype frequencies between responders and non-responders. Response was defined as "an absence of positive urine analysis, or at most, a one-time positive urine analysis for opioids during a 6-month follow-up period; nonconsumption of heroin or other types of opioid drugs according to participant self-reports; an absence of withdrawal symptoms; and a stable and regular attendance in the MMT therapeutic program". Note that the use of high-dose methadone was significantly lower in the non-responder group than in the responder group (p=0.01). This SNP was in high linkage disequilibirum with rs933271 and rs4680. Please note that alleles have been complemented to the positive strand.	Allele C is not associated with response to methadone in people with Opioid-Related Disorders as compared to allele T.	32407152	1451148012
COMT	rs933271	CC + CT	methadone	efficacy	yes	Patients with the CC or CT genotypes were significantly more likely to respond to methadone maintenance therapy (MMT) than patients with the TT genotype. Response was defined as "an absence of positive urine analysis, or at most, a one-time positive urine analysis for opioids during a 6-month follow-up period; nonconsumption of heroin or other types of opioid drugs according to participant self-reports; an absence of withdrawal symptoms; and a stable and regular attendance in the MMT therapeutic program". Note that the use of high-dose methadone was significantly lower in the non-responder group than in the responder group (p=0.01). This SNP was in high linkage disequilibirum with rs4680 and rs737866.	Genotypes CC + CT are associated with increased response to methadone in people with Opioid-Related Disorders as compared to genotype TT.	32407152	1451148002
COMT	rs4680	GG	morphine	dosage	no	Variant described as COMT 472G>A.	Genotype GG is not associated with increased dose of morphine in infants as compared to genotypes AA + AG.	25155931	1184753733
COMT	rs4633	T	risperidone	efficacy	no	The T allele was initially significantly more frequent in patients designated as non-responders to risperidone (i.e. <50% reduction in PANSS score compared to the cohort average). However, significance was lost following correction for multiple testing.	Allele T is associated with decreased response to risperidone in people with Schizophrenia as compared to allele C.	28696411	1450928150
COMT	rs165815	CT + TT	antipsychotics	efficacy	no	Patients' psychopathological symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Drugs prescribed were clozapine (58 patients), risperidone (28 patients), aripiprazole (25 patients), quetiapine (18 patients), olanzapine (12 patients), paliperidone (3 patients), ziprasidone (1 patient), fluphenazine (21 patients), zuclopenthixol (19 patients), amisulpride (13 patients), flupentixol (9 patients), promazine (7 patients), and haloperidol (3 patients).	Genotypes CT + TT are not associated with response to antipsychotics in people with Schizophrenia as compared to genotype CC.	27287786	1448258575
COMT	rs4680	A	clozapine	efficacy	no	In a subset of patients that carry the DRD4 120/120–120/240 variant, the study found a significant association of the COMT genotypes with clozapine response (P = 0.01), the A allele carriers showed a better response to clozapine [OR = 0.22; 95% confidence interval (CI) = 0.05–0.75] compared to the GG genotype.	Allele A is not associated with response to clozapine in people with Schizophrenia as compared to allele G.	29087970	1449004961
COMT	rs4680	AA	sufentanil	"dosage","efficacy"	yes		Genotype AA is associated with decreased dose of sufentanil in children as compared to genotypes AG + GG.	28006928	1449713837
COMT	rs4680	GG	opioids	dosage	yes		Genotype GG is associated with increased dose of opioids in people with Pain, Postoperative as compared to genotype AA.	25185591	1449173486
COMT	rs4818	C	opioids	dosage	no		Allele C is not associated with dose of opioids in people with Pain, Postoperative as compared to allele G.	25185591	1449173493
COMT	rs4680	G	morphine	"dosage","efficacy"	no	No association was observed between this variant and a patient's initial dose requirement or their need to escalate their dose of morphine.	Allele G is not associated with dose of morphine in people with Pain as compared to allele A.	29259946	1449182349
COMT	rs4633	C	opioids	dosage	no	Variant had no significant association with opioid dose in either the development sample or the validation sample.	Allele C is not associated with dose of opioids in people with Pain as compared to allele T.	21398039	1449715089
COMT	rs4680	A	opioids	dosage	no	Variant was significantly associated with opioid dose in the development sample, but lost significance in the validation sample.	Allele A is not associated with dose of opioids in people with Pain as compared to allele G.	21398039	1449714130
COMT	rs6269	G	morphine	"dosage","efficacy"	no	Haplotype of the six COMT variants studied in the paper was also not significantly associated with morphine dose requirements.	Allele G is not associated with dose of morphine in people with Pain, Postoperative as compared to allele A.	26902643	1449295927
COMT	rs165774	G	morphine	"dosage","efficacy"	no	Haplotype of the six COMT variants studied in the paper was also not significantly associated with morphine dose requirements.	Allele G is not associated with dose of morphine in people with Pain, Postoperative as compared to allele A.	26902643	1449295945
COMT	rs4680	AG	levodopa	dosage	no	A allele is denoted as L in the paper, while the G allele is described as the H allele.	Genotype AG is not associated with dose of levodopa in people with Parkinson Disease as compared to genotype GG.	29578580	1449576366
COMT	rs4680	AA	levodopa	dosage	no	A allele is denoted as L in the paper, while the G allele is described as the H allele.	Genotype AA is not associated with dose of levodopa in people with Parkinson Disease as compared to genotype GG.	29578580	1449576323
COMT	rs4680	AA	buprenorphine	efficacy	no	Response defined by changes in the rate of dropout from treatment between genotypes. Subsequent pairwise analysis resulted in a nominally significant association for the GG genotype compared to the AA genotype in the methadone group and the total cohort, but not in the buprenorphine group.	Genotype AA is not associated with response to buprenorphine or methadone in people with Opioid-Related Disorders as compared to genotypes AG + GG.	29333880	1449271267
COMT	rs4680	A	morphine	metabolism/PK	no		Allele A is not associated with concentrations of morphine in people with Pain, Postoperative as compared to allele G.	29474345	1449173430
COMT	rs2239393	A	tacrolimus	metabolism/PK	no	This study was attempting to validate reported variants and tacrolimus trough concentration in a large population of African American and European American kidney transplant patients.	Allele A is not associated with trough concentration of tacrolimus in people with Kidney Transplantation and Transplantation as compared to allele G.	29318894	1449163299
COMT	rs4633	C	fentanyl	dosage	no	Despite the lack of significance between this individual variant and fentanyl consumption, haplotypes of rs6269, rs4633, rs4818 and rs4680 were significantly associated with fentanyl dose. Please see the paper for further details.	Allele C is not associated with dose of fentanyl in people with Pain, Postoperative as compared to allele T.	25532715	1449716693
COMT	rs6269	A	fentanyl	dosage	no	Despite the lack of significance between this individual variant and fentanyl consumption, haplotypes of rs6269, rs4633, rs4818 and rs4680 were significantly associated with fentanyl dose. Please see the paper for further details.	Allele A is not associated with dose of fentanyl in people with Pain, Postoperative as compared to allele G.	25532715	1449716684
COMT	rs4818	C	fentanyl	dosage	no	Despite the lack of significance between this individual variant and fentanyl consumption, haplotypes of rs6269, rs4633, rs4818 and rs4680 were significantly associated with fentanyl dose. Please see the paper for further details.	Allele C is not associated with dose of fentanyl in people with Pain, Postoperative as compared to allele G.	25532715	1449716700
COMT	rs4680	A	risperidone	efficacy	no	The A allele was initially significantly more frequent in patients designated as non-responders to risperidone (i.e. <50% reduction in PANSS score compared to the cohort average). However, significance was lost following correction for multiple testing.	Allele A is associated with decreased response to risperidone in people with Schizophrenia as compared to allele G.	28696411	1450928156
COMT	rs4680	A	fentanyl	PD	no	There was no association between this variant and blood pressure, heart rate or QTc following fentanyl adminstration. Variant referred to as G472A in the paper.	Allele A is not associated with response to fentanyl in healthy individuals as compared to allele G.	30281924	1450931721
COMT	rs4818	G	risperidone	efficacy	no	The G allele was initially significantly more frequent in patients designated as responders to risperidone (i.e. >50% reduction in PANSS score compared to the cohort average). However, significance was lost following correction for multiple testing.	Allele G is associated with increased response to risperidone in people with Schizophrenia as compared to allele C.	28696411	1450928144
COMT	rs4680	GG	modafinil	efficacy	no	No significant association between this variant and Treatment Effectiveness Scores following modafinil treatment compared to placebo in Non-Hispanic Caucasian subjects.	Genotype GG is not associated with response to modafinil in people with methamphetamine dependence as compared to allele A.	22217949	1450813969
COMT	rs4680	G	morphine	"dosage","efficacy"	yes	"Patients in the fentanyl group with the COMT high-pain sensitivity haplotype (rs6269A, rs4633C, rs4818C, rs4680G) required less postoperative morphine compared with the average-pain sensitivity haplotype (rs6269A, rs4633T, rs4818C, rs4680A), but not to the low-pain sensitivity group (rs6269G, rs4633C, rs4818G, rs4680G)." High pain sensitivity haplotype is equivalent to low activity haplotype.	Allele G is associated with increased dose of morphine in people with Pain, Postoperative and Coronary Artery Disease as compared to allele A.	31967515	1451094980
COMT	rs4633	C	morphine	"dosage","efficacy"	yes	"Patients in the fentanyl group with the COMT high-pain sensitivity haplotype (rs6269A, rs4633C, rs4818C, rs4680G) required less postoperative morphine compared with the average-pain sensitivity haplotype (rs6269A, rs4633T, rs4818C, rs4680A), but not to the low-pain sensitivity group (rs6269G, rs4633C, rs4818G, rs4680G)." High pain sensitivity haplotype is equivalent to low activity haplotype.	Allele C is associated with increased dose of morphine in people with Pain, Postoperative and Coronary Artery Disease as compared to allele T.	31967515	1451094960