shlokn/autogkb huggingface dataset:
Article: Targeted pharmacogenetic analysis of antipsychotic response in the CATIE study
Gene: SKOR2
Variant/haplotype: rs9952628
Drug(s): perphenazine
Phenotype category: Efficacy
Significant: yes
Association: Allele G is associated with response to perphenazine in people with Schizophrenia.
Notes: as measured by changes in PANSS-T (positive and negative syndrome scale total score), using a mixed model repeated measures approach. Examined 6789 SNPs - p-value of p< or equal to 5x10-4 was considered significant. It was unclear whether the allele was associated with an increased or decreased response to drug.
Article: Elexacaftor-Tezacaftor-Ivacaftor in 2 cystic fibrosis adults homozygous for M1101K with end-stage lung disease
Gene: CFTR
Variant/haplotype: rs36210737
Drug(s): elexacaftor / tezacaftor / ivacaftor
Phenotype category: Efficacy
Significant: no
Association: Genotype AA is associated with increased clinical benefit to elexacaftor / tezacaftor / ivacaftor.
Notes: "We report 2 cases of pwCF with the rare M1101K variant who have improvements in lung function, pulmonary exacerbation frequency, respiratory symptoms and BMI following 6 months of ETI CFTR modulator therapy." (mapped to rs36210737AA)
Article: The Association of Transporter Genes Polymorphisms and Lung Cancer Chemotherapy Response
Gene: AQP2
Variant/haplotype: rs296766
Drug(s): platinum
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to platinum in people with Lung Neoplasms as compared to allele C.
Notes: 26 SNPs were selected which satisfied the following criteria: 1) SNPs were from HapMap Project Phase II of the Han Chinese population 2) were haplotype tagger SNPs 3) SNP minor allele frequency was higher than 5% in Han Chinese 4) the pairwise linkage disequilibrium correlation coefficient (r-squared) was greater than 0.8. After Bonferroni corrections no SNPs remained significantly associated with platinum drug efficacy.
Article: Association of SLC22A1, SLC47A1, and KCNJ11 polymorphisms with efficacy and safety of metformin and sulfonylurea combination therapy in Egyptian patients with type 2 diabetes
Gene: SLC47A1
Variant/haplotype: rs2289669
Drug(s): "metformin", "sulfonamides, urea derivatives"
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with increased clinical benefit to metformin and sulfonamides, urea derivatives in people with Diabetes Mellitus, Type 2 as compared to allele G.
Notes: "The current study found that the A allele in MATE1 rs2289669 SNP was associated with a better metformin/sulfonylurea treatment response"
Article: Genetic Variation in CYP3A43 Explains Racial Difference in Olanzapine Clearance
Gene: CYP3A43
Variant/haplotype: rs472660
Drug(s): olanzapine
Phenotype category: Dosage, Efficacy, Toxicity, Metabolism/PK
Significant: yes
Association: Genotype AA is associated with increased clearance of olanzapine in people with Schizophrenia as compared to genotypes AG + GG.
Article: Polymorphism of the complement receptor 1 gene correlates with the hematologic response to eculizumab in patients with paroxysmal nocturnal hemoglobinuria
Gene: CR1
Variant/haplotype: rs2274567
Drug(s): eculizumab
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AG + GG is associated with decreased response to eculizumab in people with paroxysmal nocturnal hemoglobinuria as compared to genotype AA.
Notes: Response was defined as no red blood cell transfusion at any time after the first 6 months on eculizumab treatment (patients had a median follow-up of 52 months, range of 11-98 months). In the paper, AA = His/His.
Article: The influence of CYP3A5 polymorphisms on haloperidol treatment in patients with alcohol addiction
Gene: CYP3A5
Variant/haplotype: rs776746
Drug(s): 6beta-hydroxycortisol
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype CT is not associated with metabolism of 6beta-hydroxycortisol in men with Alcoholism as compared to genotype CC.
Notes: No patients were found to have the TT genotype.; 6-beta-hydroxycortisol metabolism by CYP3A5 was used as a method of assessing CYP3A5 activity. No association between CYP3A5 activity and genotype at rs776746.; Please note that alleles have been complemented to the positive strand.
Article: An Intronic Variant in OPRD1 Predicts Treatment Outcome for Opioid Dependence in African-Americans
Gene: OPRD1
Variant/haplotype: rs2234918
Drug(s): buprenorphine
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to buprenorphine in people with Opioid-Related Disorders as compared to allele C.
Notes: Efficacy was determined based on the number of opioid-positive drug screens that each patient had during treatment.
Article: Influence of ADME genomic variants on tacrolimus/sirolimus blood levels and GVHD after allogeneic hematopoietic cell transplantation
Gene: ABCB1
Variant/haplotype: rs2032582
Drug(s): sirolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele A is associated with increased concentrations of sirolimus in people with hematopoietic stem cell transplantation.
Notes: Patients who were carriers of the A allele (i.e. genotypes AA, AT or AC) had higher median sirolimus levels as compared to non-A carriers (i.e. genotypes TT, CC or CT). Borderline significant findings were also observed for the dose-adjusted concentrations (C/D) of sirolimus (p=0.05). Please note that alleles have been complemented to the plus chromosomal strand.
Article: Underlying genetic structure impacts the association between CYP2B6 polymorphisms and response to efavirenz and nevirapine
Gene: CYP2B6
Variant/haplotype: rs28399499
Drug(s): efavirenz, non-nucleoside reverse transcriptase inhibitors
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to efavirenz or non-nucleoside reverse transcriptase inhibitors in women with HIV Infections as compared to genotype TT.
Article: Identification of a novel splice-site mutation in the CYP1A2 gene
Gene: CYP1A2
Variant/haplotype: CYP1A2*7
Drug(s): clozapine
Phenotype category: Toxicity, Metabolism/PK
Significant: no
Association: CYP1A2 *7 is associated with increased concentrations of clozapine in women with Schizoaffective disorder.
Notes: A 71-year-old, nonsmoking, Caucasian woman, hospitalized with a schizoaffective disorder, mania type diagnosis (ICD 10 F25.0), was suspected of presenting with an overdose of clozapine. Found to be heterozygote for CYP1A2*7. "Only one heterozygous point mutation was identified in the donor splice site of intron 6 (3534G > A) of CYP1A2. This mutation could cause abnormal RNA splicing and therefore lead to a truncated nonfunctional enzyme." Pharmvar defines *7 as 3533G>A (rs56107638, splice defect) and this variant is in no other Pharmvar CYP1A2 core star allele.
Article: Genotypic variation in the SV2C gene impacts response to atypical antipsychotics the CATIE Study
Gene: SV2C
Variant/haplotype: rs1995381
Drug(s): olanzapine
Phenotype category: Efficacy
Significant: no
Association: Genotype AA is not associated with response to olanzapine in people with Schizophrenia as compared to genotypes AG + GG.
Notes: Not significant after correction for multiple testing using the False Discovery Rate. Response was assessed by change in the total Positive and Negative Syndrome Scale (PANSS) score.
Article: β2-Adrenergic Receptor Gene Affects the Heart Rate Response of β-Blockers: Evidence From 3 Clinical Studies
Gene: ADRB1
Variant/haplotype: rs1801253
Drug(s): atenolol, metoprolol
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to atenolol or metoprolol in people with Tachycardia as compared to allele G.
Notes: No significant association between this variant and response to atenolol or metoprolol, as measured by changes in heart rate, in black or white patients.
Article: Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder
Gene: ELP5
Variant/haplotype: rs4562
Drug(s): methylphenidate
Phenotype category: Efficacy
Significant: no
Association: Allele A is associated with increased response to methylphenidate in people with Attention Deficit Disorder with Hyperactivity.
Notes: The authors carried out a GWAS in a Spanish cohort of pediatric patients, than performed a meta-analysis using data from the Spanish cohort and data from a Brazilian adult patient cohort.; This variant was not significant in the meta-analysis after Bonferroni correction had been applied, and was nominally significant (i.e did not reach genome-wide significance) in the initial GWAS in the Spanish cohort.; Response was measured on the Clinical Global Impression-Improvement scale (CGI-I). A CGI-I score of two points or less after eight weeks of treatment was considered a good response.
Article: ABC Transporter Polymorphisms are Associated with Irinotecan Pharmacokinetics and Neutropenia
Gene: UGT1A1
Variant/haplotype: rs10929302
Drug(s): SN-38
Phenotype category: Metabolism/PK
Significant: no
Association: Genotypes AG + GG are not associated with exposure to SN-38 in people with Colorectal Neoplasms as compared to genotype AA.
Notes: AUC of SN-38 was adjusted for irinotecan dose.
Article: Using EHR-Linked Biobank Data to Study Metformin Pharmacogenomics
Gene: SLC47A2
Variant/haplotype: rs4621031
Drug(s): metformin
Phenotype category: Efficacy
Significant: yes
Association: Allele C is associated with decreased response to metformin in people with Diabetes Mellitus, Type 2 as compared to allele T.
Notes: Authors looked at candidate genes in patients that had previously had genome sequencing. They look quite far outside of conventional gene boundaries. "For each candidate gene we selected SNPs 50 kb upstream and downstream of each gene using 1000 genomes project variants and NCBI build 37 as the reference genome." Table 2 shows rs4621031 as top SNP for SLC47A2
Article: Comparative performance of gene-based warfarin dosing algorithms in a multiethnic population
Gene: VKORC1
Variant/haplotype: rs9934438
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Allele A is associated with decreased dose of warfarin as compared to allele G.
Notes: Neither the addition of race, number of concurrent medications nor the number of concurrent medications interacting with warfarin enhanced algorithm performance. Similarly, consideration of CYP4F2, CALU or GGCX variant genotypes did not improve algorithms.
Article: OCT1 genetic variants influence the pharmacokinetics of morphine in children
Gene: SLC22A1
Variant/haplotype: rs34059508
Drug(s): morphine
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype AA is associated with decreased clearance of morphine in children with adenotonsillectomy as compared to genotypes AG + GG.
Notes: Children with two loss of function SLC22A1 alleles (*2 rs72552763 GAT>del, *3 rs12208357C>T, *4 rs34130495 G>A, or *5 rs34059508 G>A) were grouped together and had significantly lower clearance compared to children with the *1/*1 or *1/variant genotype.
Article: Diplotype analysis of NUDT15 variants and 6-mercaptopurine sensitivity in pediatric lymphoid neoplasms
Gene: NUDT15
Variant/haplotype: NUDT15*1, NUDT15*3, NUDT15*5
Drug(s): mercaptopurine
Phenotype category: Dosage, Toxicity
Significant: no
Association: NUDT15 *3/*3 + *3/*5 is associated with decreased dose of mercaptopurine in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to NUDT15 *1/*3 + *1/*1.
Notes: Doses were adjusted to give maintain a leukocyte count of 1500–3000 /µl. Mean dose for *1/*1, *1/*2, *1/*5 or *1/*6 was approximately 40mg/m2, and for *1/*3 was approx 20mg/m2 and for *3/*3 and *3/*5 was approx 5mg/m2.
Article: Association of BDNF, HTR2A, TPH1, SLC6A4, and COMT polymorphisms with tDCS and escitalopram efficacy: ancillary analysis of a double-blind, placebo-controlled trial
Gene: COMT
Variant/haplotype: rs4680
Drug(s): escitalopram
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to escitalopram in people with Depression as compared to allele G.
Article: Functional genetic variation in the Rev-Erbα pathway and lithium response in the treatment of bipolar disorder
Gene: GSK3B
Variant/haplotype: rs6438552
Drug(s): lithium
Phenotype category: Efficacy
Significant: no
Association: Genotype GG is associated with increased response to lithium in people with Bipolar Disorder.
Notes: Authors say not significant.
Article: Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes
Gene: C11orf65
Variant/haplotype: rs11212617
Drug(s): metformin
Phenotype category: Efficacy
Significant: not stated
Association: Allele C is associated with increased clinical benefit to metformin in people with Diabetes Mellitus, Type 2 as compared to allele A.
Notes: For the second replication set in the UK cohort (Prospective Diabetes (UKPDS) cohort), study genotyped the proxy SNP rs609261 (r2 = 0.997 with rs11212617 in 5,197 WTCCC2 controls) for technical reasons.
Article: Combined study of genetic and epigenetic biomarker risperidone treatment efficacy in Chinese Han schizophrenia patients
Gene: SLC44A3
Variant/haplotype: rs3818929
Drug(s): risperidone
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to risperidone in people with Schizophrenia as compared to allele G.
Notes: Please note that alleles have been complemented to the positive strand.
Article: Polymorphisms within methotrexate pathway genes: Relationship between plasma methotrexate levels, toxicity experienced and outcome in pediatric acute lymphoblastic leukemia
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): methotrexate
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AA + AG are associated with decreased response to methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype GG.
Notes: Please note that alleles have been complemented to the positive strand.
Article: Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder: A Genome-Wide Association Study
Variant/haplotype: rs7405404
Drug(s): lithium
Phenotype category: Efficacy
Significant: yes
Association: Allele T is associated with increased response to lithium in people with Bipolar Disorder as compared to allele C.
Article: Lack of effect of genetic polymorphisms of SLCO1B1 on the lipid-lowering response to pitavastatin in Chinese patients
Gene: SLCO1B1
Variant/haplotype: rs2306283
Drug(s): pitavastatin
Phenotype category: Efficacy
Significant: no
Association: Genotypes AG + GG are not associated with response to pitavastatin in people with Hyperlipidemias as compared to genotype AA.
Notes: There was no statistical difference among patients with wild type, SLCO1B1 388A>G or SLCO1B1 521T>C in the lipid-lowering efficacy of pitavastatin in Chinese patients with essential hyperlipidemia.
Article: Warfarin Dosage Response Related Pharmacogenetics in Chinese Population
Gene: VKORC1
Variant/haplotype: rs7294
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Genotype CC is associated with decreased concentrations of warfarin in people with heart valve replacement as compared to genotypes CT + TT.
Notes: 130 plasma samples were obtained 12 hours after the last dose of warfarin. rs7294 was associated with a significant reduction of warfarin plasma concentration (rs7294: CC 1117.29±323.23 ng/ml vs CT 1675.73±431.09 ng/ml, p < 0.001 ANOVA). rs7294 had significant effects on plasma concentration of warfarin (coefficient was 0.527, p < 0.001) and it could explain 26.7% of the variability in plasma concentration.The plasma warfarin concentrations of these samples were comparing plasma concentration within the group of patients with INR between 1.5–2.5 (n = 92). Patients were grouped according to INR and genotypes. For patients genotype CT or TT a higher plasma concentration was needed to achieve the goal INR.
Article: Polymorphisms in the VKORC1 gene are strongly associated with warfarin dosage requirements in patients receiving anticoagulation
Gene: PRSS53, VKORC1
Variant/haplotype: rs7294
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Allele T is associated with increased dose of warfarin as compared to allele C.
Article: The OPRM1 A118G polymorphism: converging evidence against associations with alcohol sensitivity and consumption
Gene: OPRM1
Variant/haplotype: rs1799971
Drug(s): ethanol
Phenotype category: Toxicity
Significant: no
Association: Allele G is not associated with response to ethanol in healthy individuals as compared to allele A.
Notes: There was no significant association between the G allele and subjective response to ethanol, craving, rate of binging or total alcohol exposure.
Article: Effect of CYP2C19*2 and *17 mutations on pharmacodynamics and kinetics of proton pump inhibitors in Caucasians
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*2
Drug(s): lansoprazole, omeprazole
Phenotype category: Metabolism/PK
Significant: no
Association: CYP2C19 *1/*1 is not associated with metabolism of lansoprazole or omeprazole in healthy individuals as compared to CYP2C19 *1/*2.
Notes: No significant difference in area under the concentration-time curve (AUC) was seen between the two genotypes in subjects taking omeprazole (10 mg/day) or lansoprazole (15 mg/day). Subjects were treated with either drug for 6 days, in a crossover fashion; AUC was measured on day 1 after initiation of treatment.
Article: Leveraging an Electronic Health Record-Linked Biorepository to Generate a Metformin Pharmacogenomics Hypothesis
Variant/haplotype: rs1920145
Drug(s): metformin
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to metformin in people with Diabetes Mellitus as compared to allele T.
Notes: EHR-linked and EHR-based phenotyping methods were used to study common variants within FMO5. Efficacy was assessed by A1c levels extracted from EHR records.
Article: Effect of SCN1Aand SCN2A gene polymorphisms on the efficacy of valproic acid treatment in Chinese children with epilepsy
Gene: SCN1A
Variant/haplotype: rs2298771
Drug(s): valproic acid
Phenotype category: Efficacy
Significant: yes
Association: Genotype TT is associated with increased clinical benefit to valproic acid in children with Epilepsy as compared to genotypes CC + CT.
Notes: "Our study found a significant association between SCN1A rs2298771 T > C and drug response in both VPA monotherapy and VPA polypharmacy. Patients carrying the rs2298771 TT genotype displayed heightened sensitivity to VPA treatment, resulting in improved seizure control compared to CT and CC genotype carriers."
Article: IFNL4 ss469415590 Variant Shows Similar Performance to rs12979860 as Predictor of Response to Treatment against Hepatitis C Virus Genotype 1 or 4 in Caucasians
Gene: IFNL3, IFNL4
Variant/haplotype: rs12979860
Drug(s): peginterferon alfa-2a, ribavirin
Phenotype category: Efficacy
Significant: yes
Association: Genotype CC is associated with increased response to peginterferon alfa-2a and ribavirin in people with Hepatitis C as compared to genotypes CT + TT.
Notes: Patients were infected with HCV genotype 1 or 4. Sustained viral response (SVR) was defined as undetectable plasma HCV RNA 24 weeks after the completion of treatment. The two SNPs rs12979860 (IL28B) and rs368234815 (IFNL4) are in strong LD (r squared of 0.82).; The SNPs were also tested by HCV genotype (1 or 4) and were both equally predictive.; The AUROC model that included rs12979860 was 0.742 (95% CI: 0.672-0.813)
Article: Implications of OPRM1 and CYP2B6 variants on treatment outcomes in methadone-maintained patients in Ontario: Exploring sex differences
Gene: OPRM1
Variant/haplotype: rs10485058
Drug(s): methadone
Phenotype category: Dosage
Significant: no
Association: Allele G is not associated with dose of methadone in people with Opioid-Related Disorders as compared to allele A.
Article: Effect of the Most Relevant CYP3A4 and CYP3A5 Polymorphisms on the Pharmacokinetic Parameters of 10 CYP3A Substrates
Gene: CYP3A4
Variant/haplotype: CYP3A4*1, CYP3A4*3, CYP3A4*20, CYP3A4*22
Drug(s): fentanyl, imatinib, quetiapine
Phenotype category: Metabolism/PK
Significant: not stated
Association: CYP3A4 *3 + *20 + *22 are associated with increased exposure to fentanyl, imatinib or quetiapine in healthy individuals as compared to CYP3A4 *1.
Notes: AUC of all three drugs was increased in the presence of CYP3A4 variants. Statistical analysis was not carried out for individual drugs due to the low number of subjects carrying CYP3A4 variants. *3 allele was identified using rs4986910, *20 was identified using rs67666821 and *22 was identified using rs35599367.
Article: Genotypic variation in the SV2C gene impacts response to atypical antipsychotics the CATIE Study
Gene: SV2C
Variant/haplotype: rs7732173
Drug(s): risperidone
Phenotype category: Efficacy
Significant: no
Association: Genotype AA is not associated with response to risperidone in people with Schizophrenia as compared to genotypes AG + GG.
Notes: Not significant after correction for multiple testing using the False Discovery Rate. Response was assessed by change in the total Positive and Negative Syndrome Scale (PANSS) score. In significant LD (r2 > 0.95) with rs10514062 and rs2358531.
Article: Association of Cytochrome P450 Genetic Variants with Clopidogrel Resistance and Outcomes in Acute Ischemic Stroke
Gene: CYP3A5
Variant/haplotype: rs776746
Drug(s): clopidogrel
Phenotype category: Efficacy
Significant: yes
Association: Genotypes CC + CT are associated with increased resistance to clopidogrel in people with Stroke as compared to genotype TT.
Notes: Frequency of CC+TC genotypes was significantly higher in clopidogrel-resistant patients than in clopidogrel-sensitive patients.
Article: Effects of CYP3A5 polymorphism on the pharmacokinetics of a once-daily modified-release tacrolimus formulation and acute kidney injury in hematopoietic stem cell transplantation
Gene: CYP3A5
Variant/haplotype: CYP3A5*1, CYP3A5*3
Drug(s): tacrolimus
Phenotype category: Dosage
Significant: yes
Association: CYP3A5 *1/*1 + *1/*3 is associated with increased dose of tacrolimus in people with hematopoietic stem cell transplantation as compared to CYP3A5 *3/*3.
Notes: Patients were started on tacrolimus continuous infusion and then converted to once-daily oral intake. Intravenous infusion of micafungin was given during the neutropenic phase, then seven days after switching from tacrolimus continuous infusion to once-daily oral intake, antifungal agents were switched from intravenous micafungin to oral azole antifungal agents. Whole blood samples from the patients were collected 4-7 days after switching to once-daily tacrolimus oral dosing and then 4-7 days after switching from intravenous micafungin to oral azole antifungals. When patients were also taking azole antifungal agents, there was a significant difference in dose. When patients were NOT taking azole antifungal agents, there was no significant difference in dose (p=0.965).
Article: The Association of Transporter Genes Polymorphisms and Lung Cancer Chemotherapy Response
Gene: TMEM205
Variant/haplotype: rs7251786
Drug(s): platinum
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to platinum in people with Lung Neoplasms as compared to allele C.
Notes: 26 SNPs were selected which satisfied the following criteria: 1) SNPs were from HapMap Project Phase II of the Han Chinese population 2) were haplotype tagger SNPs 3) SNP minor allele frequency was higher than 5% in Han Chinese 4) the pairwise linkage disequilibrium correlation coefficient (r-squared) was greater than 0.8. After Bonferroni corrections no SNPs remained significantly associated with platinum drug efficacy.