title: Global patterns of genetic diversity and signals of natural selection for human ADME genes.
abstract: Genetic polymorphisms in many genes related to drug absorption, distribution, metabolism and excretion (ADME genes) contribute to the high heterogeneity of drug responses in humans. However, the extent to which genetic variation in ADME genes may contribute to differences among human populations in drug responses has not been studied. In this work, we investigate the global distribution of genetic diversity for 31 core and 252 extended ADME genes. We find that many important ADME genes are highly differentiated across continental regions. Additionally, we analyze the genetic differentiation associated with clinically relevant, functional polymorphism alleles, which is important for evaluating potential among-population heterogeneity in drug treatment effects. We find that ADME genes show significantly greater variation in levels of population differentiation, and we find numerous signals of recent positive selection on ADME genes. These results suggest that genetic differentiation at ADME genes could contribute to population heterogeneity in drug responses.
authors.affiliation: CAS-MPG Partner Institute and Key Laboratory for Computational Biology, Shanghai Institutes for BiologicalSciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Luyong
authors.initials: L
authors.lastname: Zhang
authors.forename: Hang
authors.initials: H
authors.lastname: Zhou
authors.forename: Mark
authors.initials: M
authors.lastname: Stoneking
authors.forename: Kun
authors.initials: K
authors.lastname: Tang
mesh_terms: D000042:Absorption; D000483:Alleles; D001191:Arylamine N-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D014644:Genetic Variation; D005843:Geography; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D044469:Racial Groups / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D026901:Membrane Transport Proteins; D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System; D001191:Arylamine N-Acetyltransferase; D005982:Glutathione Transferase