shlokn/autogkb huggingface dataset:
Article: Genetic variants associated with response to lithium treatment in bipolar disorder: a genome-wide association study
Variant/haplotype: rs78015114
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.
Notes: Patients had been taking lithium for at least 6 mo. Response to lithium was assayed using the Alda scale, which quantifies symptom improvement over time. The scale is from 0-10, with 10 being the highest response score and 0 being the lowest. The authors evaluated response using a dichotomous (=7 is "responder" and < 7 is "non-responder") and a continuous phenotype (0-10). This SNP was found to be associated with improved response to lithium using the continuous phenotype but not the dichotomous phenotype measure. The association was confirmed in an independent prospective study of 73 patients.  This is one of four SNPs in LD that show association (rs79663003, rs78015114, rs74795342, rs75222709).
Article: Association between single nucleotide polymorphisms in the mu opioid receptor gene (OPRM1) and self-reported responses to alcohol in American Indians
Gene: OPRM1
Variant/haplotype: rs563649
Drug(s): ethanol
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to ethanol as compared to allele C.
Notes: Please note that alleles have been complemented to the positive strand. No significant association between this variant and any individual item or total score on the Subjective High Assessment Scale-Expectations (SHAS-E) questionnaire.
Article: Association of Pharmacogenetic Markers with Premature Discontinuation of First-line Anti-HIV Therapy: An Observational Cohort Study
Gene: NR1I2
Variant/haplotype: rs2472677
Drug(s): atazanavir, ritonavir
Phenotype category: Toxicity
Significant: no
Association: Genotypes CC + CT is not associated with increased discontinuation of atazanavir and ritonavir in people with HIV Infections as compared to genotype TT.
Notes: atazanavir boosted with ritonavir
Article: Predictors of clozapine concentration and psychiatric symptoms in patients with schizophrenia
Gene: UGT1A1
Variant/haplotype: rs34946978
Drug(s): clozapine
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele T is associated with decreased concentrations of clozapine in people with Schizophrenia or Psychotic Disorder as compared to allele C.
Notes: "In the model adjusted for clinical predictors of clozapine concentration, including smoking status and cumulative dose of clozapine, five SNPs (rs28371726 and rs202102799 in CYP2D6; rs4148323 and rs34946978 in UGT1A1; and rs2011404 in UGT1A4) showed significant associations with clozapine concentration. The rs number for each SNP associated with clozapine concentration is shown in Table 3." Table does not state which allele or direction of effect for these SNPs, so assuming minor allele and decreased concentration (beta value in table is negative).
Article: Use of Pharmacogenetic Data to Guide Individualized Opioid Prescribing After Surgery
Gene: CYP2D6
Variant/haplotype: CYP2D6 normal metabolizers
Drug(s): opioids
Phenotype category: Efficacy
Significant: no
Association: CYP2D6 normal metabolizer is associated with decreased response to opioids in people with Pain, Postoperative as compared to CYP2D6 intermediate metabolizer.
Notes: Patients with a NM phenotype had higher pain scores and opioid consumption following surgical procedures than patients with an IM phenotype. NMs also reported the least satisfaction with pain control following surgery, however, none of these association reached statistical significance. Note that the paper does not state exactly which opioids were used by patients in the study and also assigns an "intermediate to normal metabolizer" phenotype (AS 1.3-1.5). Based on the CPIC genotype to phenotype translation project, these patients would be assigned as NMs.
Article: Comprehensive Ara-C SNP score predicts leukemic cell intracellular ara-CTP levels in pediatric acute myeloid leukemia patients
Gene: CTPS1
Variant/haplotype: rs4364871
Drug(s): ara-CTP
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes CT + TT is associated with decreased concentrations of ara-CTP in children with Leukemia, Myeloid, Acute as compared to genotype CC.
Article: First genome-wide association study on rocuronium dose requirements shows association with SLCO1A2
Gene: SLCO1A2
Variant/haplotype: rs7967354
Drug(s): rocuronium
Phenotype category: Dosage
Significant: yes
Association: Genotype CC is associated with decreased dose of rocuronium in women as compared to genotypes CT + TT.
Notes: Please note that alleles have been complemented to the positive strand. Although this association is significant on its own, the authors state that the decrease in dosage requirements is best explained by the combination of the CC genotype at this position with the CC genotype at rs11045995.
Article: Clinical and genetic factors associated with warfarin maintenance dose in northern Chinese patients with mechanical heart valve replacement
Gene: VKORC1
Variant/haplotype: rs9923231
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Genotypes CT + TT are associated with decreased dose of warfarin in people with heart valve replacement as compared to genotype CC.
Article: Translesion Polymerase Genes Polymorphisms and Haplotypes Influence Survival of Osteosarcoma Patients
Gene: REV3L
Variant/haplotype: rs465646
Drug(s): cisplatin
Phenotype category: Efficacy
Significant: no
Association: Genotypes AG + GG are not associated with increased response to cisplatin in people with Osteosarcoma as compared to genotype AA.
Notes: This SNP not significantly associated with event-free survival (p = 0.601) or overall survival (p = 0.335), as determined by recurrence or death, with mean follow-up time of 143 months.
Article: Effects of a Common Eight Base Pairs Duplication at the Exon 7-Intron 7 Junction on Splicing, Expression, and Function of OCT1
Gene: SLC22A1
Variant/haplotype: rs1349294037
Drug(s): sumatriptan
Phenotype category: Other
Significant: not stated
Association: Genotype TAAGTTGT/TAAGTTGT is associated with increased concentrations of sumatriptan as compared to genotype del/del.
Notes: "The AUC of sumatriptan was slightly increased in homozygous rs35854239 duplication allele carriers compared to the wild-type (means of 7187 vs. 6277 min × ng/ ml, respectively, Figure 7A). However, this increase was not significant and was on average by 14% compared to the observed 127% increase in poor OCT1 transporters (homozygous or compound heterozygous carriers of the coding variants Arg61Cys, Gly401Ser, Gly465Arg) observed in the same study." rs35854239 was retired by dbSNP. Authors also described two other rs numbers for this indel (rs113569197 or rs36056065) also retired. We mapped this to 3 possible dbSNP identifiers that all represent indels near the end of exon 7, rs1349294037, rs755473306 and rs2114790299 but none seems to represent exactly the variants depicted in figure 1.
Article: Methadone dose in heroin-dependent patients: role of clinical factors, comedications, genetic polymorphisms and enzyme activity
Gene: CYP2B6
Variant/haplotype: rs3745274
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 T.
Notes: Methadone maintenance dose was not associated with genotype of the SNP but it was correlated to the highest dose ever used. Multiple doses versus single dose, body weight, history of cocaine dependence and ethnicity (Asian>Caucasian>African) were independently associated with methadone dose in multiple regression analysis.
Article: Association of MICA-129Met/Val polymorphism with clinical outcome of anti-TNF therapy and MICA serum levels in patients with rheumatoid arthritis
Gene: MICA
Variant/haplotype: rs1051792
Drug(s): Tumor necrosis factor alpha (TNF-alpha) inhibitors
Phenotype category: Efficacy
Significant: yes
Association: Genotype AG is associated with increased response to Tumor necrosis factor alpha (TNF-alpha) inhibitors in people with Arthritis, Rheumatoid as compared to genotypes AA + GG.
Notes: The association was significant at 3 months following treatment initiation, but significance was lost at the 6 month timepoint.
Article: ADH single nucleotide polymorphism associations with alcohol metabolism in vivo
Gene: ADH1A
Variant/haplotype: rs1229967
Drug(s): ethanol
Phenotype category: Toxicity, Metabolism/PK
Significant: yes
Association: Allele C is associated with metabolism of ethanol.
Notes: The authors did not report p-value correction for multiple hypotheses (103 snps tested).  Though they report multiple snps are significantly associated with alcohol metabolism (early or late) tested on blood or breath alcohol concentrations, this snp is NOT significant after Bonferroni correction (<0.00049).  Also, the authors did not state which alleles are associated with increased or decreased metabolism.  Instead, they simply report an association with the snp in general.  Note that this gene is on the minus strand.
Article: Novel Gene Polymorphisms for Stable Warfarin Dose in a Korean Population: Genome-Wide Association Study
Gene: FAM201A
Variant/haplotype: rs1890109
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Genotypes AG + GG is associated with increased dose of warfarin in people with heart valve replacement as compared to genotype AA.
Notes: in univariate analysis of patients on stable dose. "The VKORC1 rs9934438 allelic variation was the most influential, explaining 33.0% of dose variability, followed by FRAS1 rs4386623 at 9.9% and FAM201A rs1890109 at 4.0%."
Article: KIF6 gene as a pharmacogenetic marker for lipid-lowering effect in statin treatment
Gene: KIF6
Variant/haplotype: rs20455
Drug(s): atorvastatin
Phenotype category: Efficacy
Significant: yes
Association: Genotype GG is associated with decreased response to atorvastatin in people with Hypercholesterolemia as compared to genotype AA.
Notes: Please note that alleles have been complemented to the positive strand. A statistically significant association was seen between genotype and change in c-Non-HDL levels, but no significant association was seen between genotype and change in c-LDL or c-HDL levels.
Article: Targeted pharmacogenetic analysis of antipsychotic response in the CATIE study
Gene: PRKCE
Variant/haplotype: rs2278773
Drug(s): perphenazine
Phenotype category: Efficacy
Significant: yes
Association: Allele C 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: Effect of the Most Relevant CYP3A4 and CYP3A5 Polymorphisms on the Pharmacokinetic Parameters of 10 CYP3A Substrates
Gene: CYP3A5
Variant/haplotype: rs10264272
Drug(s): ambrisentan, aripiprazole, atorvastatin, donepezil, olanzapine
Phenotype category: Metabolism/PK
Significant: no
Association: Allele T is not associated with metabolism of ambrisentan, aripiprazole, atorvastatin, donepezil or olanzapine in healthy individuals as compared to allele C.
Notes: No significant changes in PK parameters in the presence of the C allele. The C allele is also referred to in the paper as the CYP3A5*6 allele.
Article: Integrated analysis of genetic variation and gene expression reveals novel variant for increased warfarin dose requirement in African Americans
Gene: STX1B
Variant/haplotype: rs4889606
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Genotypes AG + GG are associated with increased dose of warfarin as compared to genotype AA.
Notes: in African american patients even after conditioning on VKORC1 -1639G>A (rs9923231) variant. "Inclusion of rs4889606 genotypes, along with CYP2C9 alleles, rs9923231 genotypes, and clinical variables explained 31% of the interpatient variability in warfarin dose requirement." "The daily warfarin dose was significantly different among the three genotypes of rs4889606 with carriers of the AG or GG genotypes requiring higher doses (6.8 ±3.1 mg/day and 7.6 ±3.9 mg/day, respectively) compared to AA carriers in the Discovery (ß = 1.1; 95%CI = 0.46 – 1.8, p = 0.0009)".
Article: Assessing the Contribution of Opioid- and Dopamine-Related Genetic Polymorphisms to the Abuse Liability of Oxycodone
Gene: OPRD1
Variant/haplotype: rs2234918
Drug(s): oxycodone
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to oxycodone as compared to allele C.
Notes: No association between this variant and analgesic response to oxycodone, as assessed by cold pressor test, subjective effects of oxycodone.
Article: A Pharmacogenetics-Based Warfarin Maintenance Dosing Algorithm from Northern Chinese Patients
Gene: PROCR
Variant/haplotype: rs1415774
Drug(s): warfarin
Phenotype category: Dosage
Significant: no
Association: Allele G is not associated with dose of warfarin in people with heart valve replacement as compared to allele A.
Notes: Samples, genotypes and INRs from a cohort of 551 patients were used to derive an algorithm which was used to predict daily warfarin maintenance dose in a second cohort of 236 patients. Note: the authors state that "SNPs were tested for deviations from HWE using the chi-squared test, and for their association with the warfarin dose by Spearman correlation analysis using a *co-dominant* model."
Article: Association between opioid receptor mu 1 (OPRM1) gene polymorphisms and tobacco and alcohol consumption in a Spanish population
Gene: OPRM1
Variant/haplotype: rs1799971
Drug(s): nicotine
Phenotype category: Dosage
Significant: no
Association: Genotypes AG + GG are not associated with dose of nicotine as compared to genotype AA.
Notes: No significant association between this variant and tobacco consumption.
Article: The International SSRI Pharmacogenomics Consortium (ISPC): a genome-wide association study of antidepressant treatment response
Gene: RND1
Variant/haplotype: rs2453488
Drug(s): Selective serotonin reuptake inhibitors
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to Selective serotonin reuptake inhibitors in people with Depressive Disorder, Major as compared to allele C.
Notes: The allele did not reach genome wide significance in the discovery or replication cohorts. GWA analyses were performed for two phenotypes: ‘% change in HRSD-17 score’ (% HRSD defined as the change in HRSD-17 score divided by the baseline score) and ‘response’ (defined as greater than or equal to 50% reduction in HRSD-17 score from baseline to 4-week visit). Please note, alleles have been complemented to the + chromosomal strand.
Article: Exploring the multifactorial nature of postoperative nausea and vomiting in women following surgery for breast cancer
Gene: COMT
Variant/haplotype: rs4680
Drug(s): opioids
Phenotype category: Dosage
Significant: yes
Association: Genotype GG is associated with increased dose of opioids in women with Breast Neoplasms and Pain, Postoperative as compared to genotypes AA + AG.
Notes: 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.
Article: Assessing the Contribution of Opioid- and Dopamine-Related Genetic Polymorphisms to the Abuse Liability of Oxycodone
Gene: OPRD1
Variant/haplotype: rs581111
Drug(s): oxycodone
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AA + AG are associated with decreased response to oxycodone as compared to genotype GG.
Notes: Subjects with the AA or AG genotypes had a decreased subjective 'High Quality' response to oxycodone than subjects with the GG genotype. Authors note that this was an interaction with rs6848893. Please note that alleles have been complemented to the positive strand.
Article: Genetic polymorphisms in human CYP2A6 gene causing impaired nicotine metabolism
Gene: CYP2A6
Variant/haplotype: rs28399468
Drug(s): nicotine
Phenotype category: Other, Metabolism/PK
Significant: no
Association: Allele A is associated with decreased metabolism of nicotine as compared to allele C.
Notes: This SNP is in the CYP2A6*8 and *10 allele. Individuals with *4, *7, *10 alleles had impaired nicotine metabolism in this study. Statistics compared metabolism levels in Japanese and Korean subjects, rather than this allele compared to wildtype.
Article: Meta-Analysis on Pharmacogenetics of Platinum-Based Chemotherapy in Non Small Cell Lung Cancer (NSCLC) Patients
Gene: XRCC1
Variant/haplotype: rs25487
Drug(s): Platinum compounds
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with increased response to Platinum compounds in people with Carcinoma, Non-Small-Cell Lung as compared to allele T.
Notes: No significant relationship between genotype and drug response was detected.
Article: Genetic polymorphisms to identify patients with an optimal response to tildrakizumab in psoriasis patients from real‐life clinical practice
Gene: PDE4D
Variant/haplotype: rs10556657
Drug(s): tildrakizumab
Phenotype category: Efficacy
Significant: yes
Association: Genotype CT/CT is associated with decreased clinical benefit to tildrakizumab in people with Psoriasis as compared to genotypes CT/CTGTCT + CTGTCT/CTGTCT.
Notes: "Our data also suggest that patients carrying the genotype GG for rs610604 (TNFAIP3), CTGT/− for rs72167053 (PDE4D) and CT for rs9373839 (ATG5) had a higher probability to not achieve PASI ≤1 after 12 months of tildrakizumab treatment, while those with CT for rs708567 (IL17RC) have a higher chance to have an optimal response to this treatment." rs10556657 is new identifier for rs72167053 (PDE4D) Tables 2and  3 and figure 1 show it is the homozygous deletion that is associated with risk of treatment non-response rather than heterozygotes.
Article: OPRM1, OPRK1 and COMT Genetic Polymorphisms Associated with Opioid Effects on Experimental Pain: A Randomized, Double-Blind, Placebo-Controlled Study
Gene: OPRK1
Variant/haplotype: rs1051660
Drug(s): morphine
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to morphine in healthy individuals as compared to allele C.
Notes: Study-wide significance was set to p<0.017.
Article: Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder
Gene: PIGM
Variant/haplotype: rs12409352
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: G PROTEIN RECEPTOR KINASE 4 (GRK4) POLYMORPHISMS: BETA-BLOCKER PHARMACOGENETICS AND TREATMENT RELATED OUTCOMES IN HYPERTENSION
Gene: GRK4
Variant/haplotype: rs1801058
Drug(s): atenolol
Phenotype category: Efficacy
Significant: no
Association: Allele T is associated with decreased response to atenolol in people with Hypertension as compared to allele C.
Notes: This was described as a trend but not significant.
Article: The Distribution of the Genotypes of ABCB1 and CES1 Polymorphisms in Kazakhstani Patients with Atrial Fibrillation Treated with DOAC
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): dabigatran
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is not associated with decreased dose-adjusted trough concentrations of dabigatran in people with Atrial Fibrillation as compared to allele G.
Article: Genetic Polymorphisms of ENPP2 Are Possibly Associated with Pain Severity and Opioid Dose Requirements in Patients with Inflammatory Pain Conditions: Clinical Observation Study
Gene: ENPP2
Variant/haplotype: rs7832704
Drug(s): opioids
Phenotype category: Dosage
Significant: yes
Association: Genotype AA is associated with increased dose of opioids in people with Pain, Postoperative as compared to genotypes AG + GG.
Notes: authors describe for minor allele, all sources in ALFA give A as minor allele and G as major allele. It was also significant in the allelic model. This was not significant for dosage in the cancer pain intensity cohort.
Article: Using EHR-Linked Biobank Data to Study Metformin Pharmacogenomics
Gene: PRKAG2
Variant/haplotype: rs4725434
Drug(s): metformin
Phenotype category: Efficacy
Significant: yes
Association: Allele T is associated with increased response to metformin in people with Diabetes Mellitus, Type 2 as compared to allele C.
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 rs4725434 as top SNP for PRKAG2
Article: Valproic acid levels in neurodevelopmental disorders: correlation with CYP and SULT genes using LC-MS/MS
Gene: CYP2D6
Variant/haplotype: CYP2D6*4, CYP2D6*10
Drug(s): valproic acid
Phenotype category: Metabolism/PK
Significant: no
Association: CYP2D6 *4 + *10 is not associated with increased concentrations of valproic acid in people with Autism or Intellectual Disability.
Notes: "No significant correlation was observed between VPA plasma concentrations and genotypes of SULT1A1 (p = 0.522), CYP2C192 (p = 0.288), CYP2D64 (p = 0.895), or CYP2D6*10 (p = 0.067)." There was one individual with *10 who also carried *4 and had "Slightly high" TDM concentrations. One other individual was heterozygous *4 (also CYP2C19*2) and had toxic TDM concentrations.
Article: Effect of NAT2, GSTM1 and CYP2E1 genetic polymorphisms on plasma concentration of isoniazid and its metabolites in patients with tuberculosis, and the assessment of exposure-response relationships
Gene: GSTM1
Variant/haplotype: GSTM1 non-null, GSTM1 null
Drug(s): isoniazid
Phenotype category: Metabolism/PK
Significant: no
Association: GSTM1 null is not associated with increased concentrations of isoniazid in people with Tuberculosis as compared to GSTM1 non-null.
Notes: "None of pharmacokinetic parameters differed; significantly between GSTM1-plus and -null genotypes."
Article: Pharmacogenetics of TNF inhibitor response in rheumatoid arthritis utilizing the two-component disease activity score
Gene: ALPL
Variant/haplotype: rs885814
Drug(s): adalimumab, certolizumab pegol, etanercept, infliximab, Tumor necrosis factor alpha (TNF-alpha) inhibitors
Phenotype category: Efficacy
Significant: yes
Association: Allele T is associated with decreased response to adalimumab, certolizumab pegol, etanercept, infliximab or Tumor necrosis factor alpha (TNF-alpha) inhibitors in people with Arthritis, Rheumatoid as compared to allele C.
Notes: as measured by change in 2C-DAS28. Table 2 shows change was a positive value for this variant suggesting increased 2C-DAS28 and less response, it was not attributed to a particular allele at this rs number location so assumed minor allele based on dbSNP frequencies.