{"entity": "researcher", "timestamp": "2026-11-06T19:21:03.064Z", "family": "Tremmel", "given": "Roman", "initials": "R", "orcid": "0000-0003-1564-0433", "affiliations": ["Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.", "University T\u00fcbingen, T\u00fcbingen, Germany."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/5dcfb9d17c9340d69ea2c5fcbd06aeec.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/5dcfb9d17c9340d69ea2c5fcbd06aeec"}}, "publications": [{"entity": "publication", "iuid": "b8e28bb7e0924bc890d6b2c2d625a78c", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/b8e28bb7e0924bc890d6b2c2d625a78c.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/b8e28bb7e0924bc890d6b2c2d625a78c"}}, "title": "PharmFreq: a comprehensive atlas of ethnogeographic allelic variation in clinically important pharmacogenes.", "authors": [{"family": "Tremmel", "given": "Roman", "initials": "R", "orcid": "0000-0003-1564-0433", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5dcfb9d17c9340d69ea2c5fcbd06aeec.json"}}, {"family": "Zhou", "given": "Yitian", "initials": "Y", "orcid": "0000-0003-3066-5444", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c4e92db79d554ad283927ad7e6e54e8d.json"}}, {"family": "Camara", "given": "Mahamadou D", "initials": "MD"}, {"family": "Laarif", "given": "Sofiene", "initials": "S"}, {"family": "Eliasson", "given": "Erik", "initials": "E"}, {"family": "Lauschke", "given": "Volker M", "initials": "VM", "orcid": "0000-0002-1140-6204", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/82048d4da61547d08aa9d2bb3bae12dd.json"}}], "type": "journal article", "published": "2025-01-06", "journal": {"title": "Nucleic Acids Res.", "issn": "1362-4962", "volume": "53", "issue": "D1", "pages": "D1498-D1509", "issn-l": "0305-1048"}, "abstract": "Genetic polymorphisms in drug metabolizing enzymes, drug transporters as well as in genes encoding the human major histocompatibility complex contribute to inter-individual differences in drug efficacy and safety. The extent, pattern and complexity of such pharmacogenetic variation differ drastically across human populations. Here, we present PharmFreq, a global repository of pharmacogenetic frequency information that aggregates frequency data of 658 allelic variants from over 10 million individuals collected from >1200 studies across 144 countries. Most investigations were conducted in East Asian and European populations, accounting for 29.4 and 26.6% of all studies, respectively. We find that the number of studies per country and aggregated cohort size correlated significantly with population size (R = 0.55, P= 3*10-9) and country gross domestic product (R = 0.43, P= 2*10-6) with overall population coverage varying between 5% in Estonia to < 0.001% in many countries in Sub-Saharan Africa and Asia. All frequency data are openly accessible via a web-based interactive dashboard at pharmfreq.com that facilitates the exploration, visualization and analysis of country- and population-specific data and their inferred phenotypic consequences. PharmFreq thus presents a comprehensive, freely available resource for pharmacogenetic variant frequencies that can inform about ethnogeographic pharmacogenomic diversity and reveal important inequities that help to focus future research efforts into underrepresented populations.", "doi": "10.1093/nar/gkae1016", "pmid": "39540424", "labels": {"DDLS Fellow": null, "Yitian Zhou": null}, "xrefs": [{"db": "pmc", "key": "PMC11701539"}, {"db": "pii", "key": "7900193"}], "notes": [], "created": "2026-11-06T09:35:20.571Z", "modified": "2026-11-06T09:35:20.615Z"}, {"entity": "publication", "iuid": "f15ea5379f604dd5afc828e8ac6553fb", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/f15ea5379f604dd5afc828e8ac6553fb.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/f15ea5379f604dd5afc828e8ac6553fb"}}, "title": "Structural variation of the coding and non-coding human pharmacogenome.", "authors": [{"family": "Tremmel", "given": "Roman", "initials": "R", "orcid": "0000-0003-1564-0433", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5dcfb9d17c9340d69ea2c5fcbd06aeec.json"}}, {"family": "Zhou", "given": "Yitian", "initials": "Y"}, {"family": "Schwab", "given": "Matthias", "initials": "M", "orcid": "0000-0002-9984-075X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a671991e1b85463e8a7bbad2e29fb1bd.json"}}, {"family": "Lauschke", "given": "Volker M", "initials": "VM", "orcid": "0000-0002-1140-6204", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/82048d4da61547d08aa9d2bb3bae12dd.json"}}], "type": "journal article", "published": "2023-09-08", "journal": {"title": "NPJ Genom Med", "issn": "2056-7944", "volume": "8", "issue": "1", "pages": "24", "issn-l": null}, "abstract": "Genetic variants in drug targets and genes encoding factors involved in drug absorption, distribution, metabolism and excretion (ADME) can have pronounced impacts on drug pharmacokinetics, response, and toxicity. While the landscape of genetic variability at the level of single nucleotide variants (SNVs) has been extensively studied in these pharmacogenetic loci, their structural variation is only poorly understood. Thus, we systematically analyzed the genetic structural variability across 908 pharmacogenes (344 ADME genes and 564 drug targets) based on publicly available whole genome sequencing data from 10,847 unrelated individuals. Overall, we extracted 14,984 distinct structural variants (SVs) ranging in size from 50 bp to 106 Mb. Each individual harbored on average 10.3 and 1.5 SVs with putative functional effects that affected the coding regions of ADME genes and drug targets, respectively. In addition, by cross-referencing pharmacogenomic SVs with experimentally determined binding data of 224 transcription factors across 130 cell types, we identified 1276 non-coding SVs that overlapped with gene regulatory elements. Based on these data, we estimate that non-coding structural variants account for 22% of the genetically encoded pharmacogenomic variability. Combined, these analyses provide the first comprehensive map of structural variability across pharmacogenes, derive estimates for the functional impact of non-coding SVs and incentivize the incorporation of structural genomic data into personalized drug response predictions.", "doi": "10.1038/s41525-023-00371-y", "pmid": "37684227", "labels": {"DDLS Fellow": null, "Yitian Zhou": null}, "xrefs": [{"db": "pmc", "key": "PMC10491600"}, {"db": "pii", "key": "10.1038/s41525-023-00371-y"}], "notes": [], "created": "2026-11-06T09:33:14.437Z", "modified": "2026-11-06T09:33:14.477Z"}, {"entity": "publication", "iuid": "28a34a109dc24e86a66f6d9edaed4d04", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/28a34a109dc24e86a66f6d9edaed4d04.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/28a34a109dc24e86a66f6d9edaed4d04"}}, "title": "Cross-Ancestry Genome-Wide Association Study Defines the Extended CYP2D6 Locus as the Principal Genetic Determinant of Endoxifen Plasma Concentrations.", "authors": [{"family": "Khor", "given": "Chiea Chuen", "initials": "CC"}, {"family": "Winter", "given": "Stefan", "initials": "S"}, {"family": "Sutiman", "given": "Natalia", "initials": "N"}, {"family": "M\u00fcrdter", "given": "Thomas E", "initials": "TE"}, {"family": "Chen", "given": "Sylvia", "initials": "S", "orcid": "0000-0002-0445-6502", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5310f9983f7c447b8ccd17d80cb2d4a3.json"}}, {"family": "Lim", "given": "Joanne Siok Liu", "initials": "JSL"}, {"family": "Li", "given": "Zheng", "initials": "Z", "orcid": "0000-0002-7060-2213", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a014baeffa7c4317af45a704a24d17c9.json"}}, {"family": "Li", "given": "Jingmei", "initials": "J", "orcid": "0000-0001-8587-7511", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6027dea1185b4a00a77a6bca138eab20.json"}}, {"family": "Sim", "given": "Kar Seng", "initials": "KS", "orcid": "0000-0002-3822-7759", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7f1c9943279444bfad3e051f04296a71.json"}}, {"family": "Ganchev", "given": "Boian", "initials": "B"}, {"family": "Eccles", "given": "Diana", "initials": "D"}, {"family": "Eccles", "given": "Bryony", "initials": "B"}, {"family": "Tapper", "given": "William", "initials": "W"}, {"family": "Zgheib", "given": "Nathalie K", "initials": "NK", "orcid": "0000-0002-0571-768X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/191f804995e74a6d91b2c3a150be69ee.json"}}, {"family": "Tfayli", "given": "Arafat", "initials": "A"}, {"family": "Ng", "given": "Raymond Chee Hui", "initials": "RCH"}, {"family": "Yap", "given": "Yoon Sim", "initials": "YS"}, {"family": "Lim", "given": "Elaine", "initials": "E"}, {"family": "Wong", "given": "Mabel", "initials": "M"}, {"family": "Wong", "given": "Nan Soon", "initials": "NS"}, {"family": "Ang", "given": "Peter Cher Siang", "initials": "PCS"}, {"family": "Dent", "given": "Rebecca", "initials": "R"}, {"family": "Tremmel", "given": "Roman", "initials": "R", "orcid": "0000-0003-1564-0433", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5dcfb9d17c9340d69ea2c5fcbd06aeec.json"}}, {"family": "Klein", "given": "Kathrin", "initials": "K"}, {"family": "Schaeffeler", "given": "Elke", "initials": "E"}, {"family": "Zhou", "given": "Yitian", "initials": "Y", "orcid": "0000-0003-3066-5444", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c4e92db79d554ad283927ad7e6e54e8d.json"}}, {"family": "Lauschke", "given": "Volker M", "initials": "VM", "orcid": "0000-0002-1140-6204", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/82048d4da61547d08aa9d2bb3bae12dd.json"}}, {"family": "Eichelbaum", "given": "Michel", "initials": "M"}, {"family": "Schwab", "given": "Matthias", "initials": "M", "orcid": "0000-0002-9984-075X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a671991e1b85463e8a7bbad2e29fb1bd.json"}}, {"family": "Brauch", "given": "Hiltrud B", "initials": "HB", "orcid": "0000-0001-7531-2736", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d50df7befe8b45989a8b81d3051004b5.json"}}, {"family": "Chowbay", "given": "Balram", "initials": "B", "orcid": "0000-0003-4775-9877", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a4b56e6cd97f40cd88668603d7c510f6.json"}}, {"family": "Schroth", "given": "Werner", "initials": "W", "orcid": "0000-0003-1412-4592", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/30be50cbd1474b8ebe8a0b31c5b47c91.json"}}], "type": "journal article", "published": "2023-03-00", "journal": {"title": "Clin. Pharmacol. Ther.", "issn": "1532-6535", "volume": "113", "issue": "3", "pages": "712-723", "issn-l": "0009-9236"}, "abstract": "The therapeutic efficacy of tamoxifen is predominantly mediated by its active metabolites 4-hydroxy-tamoxifen and endoxifen, whose formation is catalyzed by the polymorphic cytochrome P450 2D6 (CYP2D6). Yet, known CYP2D6 polymorphisms only partially determine metabolite concentrations in vivo. We performed the first cross-ancestry genome-wide association study with well-characterized patients of European, Middle-Eastern, and Asian descent (n = 497) to identify genetic factors impacting active and parent metabolite formation. Genome-wide significant variants were functionally evaluated in an independent liver cohort (n = 149) and in silico. Metabolite prediction models were validated in two independent European breast cancer cohorts (n = 287, n = 189). Within a single 1-megabase (Mb) region of chromosome 22q13 encompassing the CYP2D6 gene, 589 variants were significantly associated with tamoxifen metabolite concentrations, particularly endoxifen and metabolic ratio (MR) endoxifen/N-desmethyltamoxifen (minimal P = 5.4E-35 and 2.5E-65, respectively). Previously suggested other loci were not confirmed. Functional analyses revealed 66% of associated, mostly intergenic variants to be significantly correlated with hepatic CYP2D6 activity or expression (\u03c1 = 0.35 to -0.52), and six hotspot regions in the extended 22q13 locus impacting gene regulatory function. Machine learning models based on hotspot variants (n = 12) plus CYP2D6 activity score (AS) increased the explained variability (~ 9%) compared with AS alone, explaining up to 49% (median R2 ) and 72% of the variability in endoxifen and MR endoxifen/N-desmethyltamoxifen, respectively. Our findings suggest that the extended CYP2D6 locus at 22q13 is the principal genetic determinant of endoxifen plasma concentration. Long-distance haplotypes connecting CYP2D6 with adjacent regulatory sites and nongenetic factors may account for the unexplained portion of variability.", "doi": "10.1002/cpt.2846", "pmid": "36629403", "labels": {"DDLS Fellow": null, "Yitian Zhou": null}, "xrefs": [], "notes": [], "created": "2026-11-06T09:32:58.404Z", "modified": "2026-11-06T09:32:59.085Z"}]}