Genomes and Genes
Allen D Roses
Affiliation: Duke University Medical Center
- Age at onset in two common neurodegenerative diseases is genetically controlledYi Ju Li
Department of Medicine, Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA
Am J Hum Genet 70:985-93. 2002..62. These data suggest that a common gene affects AAO in these two common complex neurodegenerative diseases...
- A genomewide scan for early-onset coronary artery disease in 438 families: the GENECARD StudyElizabeth R Hauser
Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA
Am J Hum Genet 75:436-47. 2004..These data provide initial areas of the human genome where further investigation may reveal susceptibility genes for early-onset CAD...
- On the utility of data from the International HapMap Project for Australian association studiesJim Stankovich
Division of Genetics and Bioinformatics, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, 3050 Parkville, Victoria, Australia
Hum Genet 119:220-2. 2006..Patterns of LD in the Australian and HapMap samples are similar, and tag SNPs chosen using HapMap genotypes perform almost as well on Australian samples as tags chosen using Australian genotypes...
- Use of whole-genome association scans in disease gene identification, drug discovery and developmentAllen D Roses
Duke University, R David Thomas Center, 1 Towerview Drive, Suite 343, Box 90120, Durham, NC 27708, USA
IDrugs 10:797-804. 2007..This feature article discusses the use of whole-genome association scans in disease gene identification, drug discovery and development...
- Candidate single-nucleotide polymorphisms from a genomewide association study of Alzheimer diseaseHao Li
GlaxoSmithKline, Research Triangle Park, North Carolina, USA
Arch Neurol 65:45-53. 2008..To identify single-nucleotide polymorphisms (SNPs) associated with risk and age at onset of Alzheimer disease (AD) in a genomewide association study of 469 438 SNPs...
- A TOMM40 variable-length polymorphism predicts the age of late-onset Alzheimer's diseaseA D Roses
Department of Medicine, Duke University, Durham, NC 27708 0120, USA
Pharmacogenomics J 10:375-84. 2010..In addition, these results show the effective use of a phylogenetic approach for analysis of haplotypes of polymorphisms, including structural polymorphisms, which contribute to complex diseases...
- Pharmacogenetics in drug discovery and development: a translational perspectiveAllen D Roses
Deane Drug Discovery Institute, Duke University Medical Center and Fuqua School of Business, Durham, North Carolina 27708, USA
Nat Rev Drug Discov 7:807-17. 2008....
- An inherited variable poly-T repeat genotype in TOMM40 in Alzheimer diseaseAllen D Roses
Department of Neurobiology and Neurology and the Deane Drug Discovery Institute, Duke University, Durham, North Carolina 27708, USA
Arch Neurol 67:536-41. 2010..Additional data will further refine the relationship between the length of the poly-T alleles and age at disease onset and determine if the relationship is linear...
- Commentary on "a roadmap for the prevention of dementia: the inaugural Leon Thal Symposium." An impending prevention clinical trial for Alzheimer's disease: roadmaps and realitiesAllen D Roses
Duke University Medical Center and the Fuqua School of Business, Durham, NC, USA
Alzheimers Dement 4:164-6. 2008
- Stimulation of cholecystokinin-A receptors with Gl181771X: a failed clinical trial that did not test the pharmacogenetic hypothesis for reduction of food intakeA D Roses
Deane Drug Discovery Institute, Institute for Genomic Sciences and Policy, Duke University School of Medicine and Fuqua School of Business, Durham, North Carolina, USA
Clin Pharmacol Ther 85:362-5. 2009..The hypotheses should have been based on the original putative role of a central mechanism affecting appetite, which had been validated using efficacy PGx in phase IIA...
- Comprehensive association analysis of APOE regulatory region polymorphisms in Alzheimer diseaseKristin K Nicodemus
Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, North Carolina 27710, USA
Neurogenetics 5:201-8. 2004..In conclusion, SNPs +5361, or a SNP in strong linkage disequilibrium, may confer some additional risk for developing AD beyond the risk due to APOE-4; however, the effect independent of APOE-4 is likely to be small...
- Ordered-subsets linkage analysis detects novel Alzheimer disease loci on chromosomes 2q34 and 15q22William K Scott
Department of Medicine, Duke University Medical Center, and Center for Human Genetics, Institute for Genome Sciences and Policy, Duke University, Durham, NC 27710, USA
Am J Hum Genet 73:1041-51. 2003..These results indicate that linkage to chromosome 9p is strongest in late-onset AD and that regions on chromosome 2q34 and 15q22 are linked to early-onset AD and very-late-onset AD, respectively...
- Genetic variation at a single locus and age of onset for Alzheimer's diseaseMichael W Lutz
Deane Drug Discovery Institute, Duke University, Durham, NC, USA
Alzheimers Dement 6:125-31. 2010....
- Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson diseaseYi Ju Li
Department of Medicine, Center for Human Genetics, Institute for Genome Science and Policy, Duke University Medical Center, Box 3445, Durham, NC 27710, USA
Hum Mol Genet 12:3259-67. 2003..This is provocative given reports of the possible role of inflammation in these two neurodegenerative disorders...
- TOMM40 and APOE: Requirements for replication studies of association with age of disease onset and enrichment of a clinical trialAllen D Roses
Duke University, Durham, NC, USA Zinfandel Pharmaceuticals, Durham, NC, USA
Alzheimers Dement 9:132-6. 2013..This is true when assessing potential biomarkers for age of onset and when assessing the therapeutic potential of medicines that may delay the onset or progression of this disease...
- A homopolymer polymorphism in the TOMM40 gene contributes to cognitive performance in agingKathleen M Hayden
Joseph and Kathleen Bryan Alzheimer s Disease Research Center, Duke University, Durham, NC, USA
Alzheimers Dement 8:381-8. 2012..A highly polymorphic T homopolymer was recently found to be associated with late-onset Alzheimer's disease risk and age of onset...
- Analysis of European mitochondrial haplogroups with Alzheimer disease riskJoelle M van der Walt
Department of Medicine, Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA
Neurosci Lett 365:28-32. 2004..We suggest that variations within haplogroup U may be involved in AD expression in combination with environmental exposures or nuclear proteins other than APOE...
- Pleiotropy and allelic heterogeneity in the TOMM40-APOE genomic region related to clinical and metabolic features of hepatitis C infectionOrnit Chiba-Falek
Division of Neurology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
Hum Genet 131:1911-20. 2012..In CHC patients, genetic heterogeneity in the APOE/TOMM40 genomic region is significantly associated with variation in serum ApoE and ApoB levels, and also with fibrosis suggesting a pleiotropic attribute of this genomic region...
- Characterization of the poly-T variant in the TOMM40 gene in diverse populationsColton Linnertz
Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina, United States of America
PLoS ONE 7:e30994. 2012..These data may be used as references for '523' allele and '523'-APOE haplotype frequencies in diverse populations for the design of research studies and clinical trials...
- Genome-wide scan of copy number variation in late-onset Alzheimer's diseaseErin L Heinzen
Institute for Genome Sciences and Policy, Center for Human Genome Variation, Duke University Medical Center, Durham, NC 27708, USA
J Alzheimers Dis 19:69-77. 2010..In this analysis, no new SNPs show genome-wide significance. We also screened for effects of copy number variation, and while nothing was significant, a duplication in CHRNA7 appears interesting enough to warrant further investigation...
- New applications of disease genetics and pharmacogenetics to drug developmentAllen D Roses
Zinfandel Pharmaceuticals, Inc, Durham, NC, United States Duke University Medical Center, Department of Neurology, Durham, NC, United States Electronic address
Curr Opin Pharmacol 14:81-9. 2014..The trial is made practical by the use of a pharmacogenetic algorithm based on TOMM40 and APOE genotypes and age to identify normal subjects at high risk of MCI-AD between the ages of 65-83 years within a five year follow-up period. ..
- The Q7R Saitohin gene polymorphism is not associated with Alzheimer diseaseSofia A Oliveira
Department of Medicine and Center for Human Genetics, Institute for Genome Sciences and Policy, Box 3445, Duke University Medical Center, Durham, NC 27710, USA
Neurosci Lett 347:143-6. 2003..We found no evidence of significant association of this polymorphism with risk of AD using family-based and case-control tests of association...
- The medical and economic roles of pipeline pharmacogenetics: Alzheimer's disease as a model of efficacy and HLA-B(*)5701 as a model of safetyAllen D Roses
Deane Drug Discovery Institute, Institute for Genomic Sciences and Policy, Duke University, Durham, NC 27708, USA
Neuropsychopharmacology 34:6-17. 2009..Targeting of medicines during drug development is now possible, practical, and profitable...
- Design of the Genetics of Early Onset Cardiovascular Disease (GENECARD) studyElizabeth R Hauser
Duke University Medical Center, Durham, NC 27710, USA
Am Heart J 145:602-13. 2003..Early onset (premature) coronary artery disease (EOCAD) is known to have a particularly strong genetic component. However, the actual genes leading to this increased risk of CAD remain obscure...
- A genome-wide investigation of SNPs and CNVs in schizophreniaAnna C Need
Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina, USA
PLoS Genet 5:e1000373. 2009..On balance, these data suggest that very few schizophrenia patients share identical genomic causation, potentially complicating efforts to personalize treatment regimens...
- The Population Reference Sample, POPRES: a resource for population, disease, and pharmacological genetics researchMatthew R Nelson
GlaxoSmithKline, Research Triangle Park, NC 27709, USA
Am J Hum Genet 83:347-58. 2008..The genotype and demographic data from this reference sample are freely available through the NCBI database of Genotypes and Phenotypes (dbGaP)...
- On the discovery of the genetic association of Apolipoprotein E genotypes and common late-onset Alzheimer diseaseAllen D Roses
Genetic Research, GlaxoSmithKline Research and Development, Five Moore Drive, 5 5616, Research Triangle Park, NC 27709, USA
J Alzheimers Dis 9:361-6. 2006..Rosiglitazone, a PPARgamma agonist which also leads to mitochondrial proliferation shown efficacy as a monotherapy in a Phase IIB clinical trial of 511 patients in an APOE allele-specific analysis...
- Genome-based pharmacogenetics and the pharmaceutical industryAllen D Roses
GlaxoSmithKline, Five Moore Drive, Research Triangle Park, North Carolina 27709, USA
Nat Rev Drug Discov 1:541-9. 2002....
- Medical applications of haplotype-based SNP maps: learning to walk before we runEric Lai
Nat Genet 32:353. 2002
- Drug development and Alzheimer diseaseAllen D Roses
GlaxoSmithKline Research and Development, Genetics Research, Neurology Centre for Excellence in Drug Discovery, Research Triangle Park, NC 27709, USA
Am J Geriatr Psychiatry 11:123-30. 2003
- Association of genetic variations in HLA-B region with hypersensitivity to abacavir in some, but not all, populationsArlene R Hughes
GlaxoSmithKline, NC 27709, USA
Pharmacogenomics 5:203-11. 2004..Even after a marker set is identified, appropriate clinical identification and management of hypersensitivity to abacavir must remain the cornerstone of clinical practice...
- Pharmacogenetics to predict drug-related adverse eventsDavid A Hosford
Department of Genetics Research, GlaxoSmithKline R and D, Research Triangle Park, North Carolina 27709, USA
Toxicol Pathol 32:9-12. 2004..Together, these studies demonstrate in a stepwise manner the feasibility of using pharmacogenetic approaches to predict DRAEs...
- Pharmacogenetics place in modern medical science and practiceAllen D Roses
Genetics Research, GlaxoSmithKline, Research Triangle Park, NC 27709, USA
Life Sci 70:1471-80. 2002..Pharmacogenetics has the potential of changing the pipeline model of drug discovery, clinical development, and mass customization marketing...
- Applying technologies towards safe and effective medicinesAllen D Roses
GlaxoSmithKline, Research Triangle Park, NC 27709, USA
Biotechniques 39:563-4. 2005
- ApoE4 impairs hippocampal plasticity isoform-specifically and blocks the environmental stimulation of synaptogenesis and memoryOfir Levi
The Department of Neurobiochemistry, The George S Wise Faculty of Life Sciences, Tel Aviv University, 69978, Ramat Aviv, Israel
Neurobiol Dis 13:273-82. 2003..This provides a novel mechanism by which environmental factors can modulate the function and phenotypic expression of the apoE genotype...
- Genetic variations in HLA-B region and hypersensitivity reactions to abacavirSeth Hetherington
HIV Clinical Development and Medical Affairs, GlaxoSmithKline, Research Triangle Park, NC 27709, USA
Lancet 359:1121-2. 2002..Clinical monitoring and management of hypersensitivity reactions among patients receiving abacavir must remain unchanged...
- Replication study of the insulin receptor gene in migraine with auraChristian Netzer
Institute of Human Genetics, University of Cologne, 50931 Cologne, Germany
Genomics 91:503-7. 2008..005. In conclusion, further association studies for rs2860174 with even larger numbers of individuals are required to exclude or confirm definitely a small effect of this SNP on migraine susceptibility...
- Identification of miRNA changes in Alzheimer's disease brain and CSF yields putative biomarkers and insights into disease pathwaysJohn P Cogswell
Department of Pharmacogenetics, GlaxoSmithKline Inc, Research Triangle Park, NC 27709, USA
J Alzheimers Dis 14:27-41. 2008..We additionally recovered miRNAs from cerebrospinal fluid and discovered AD-specific miRNA changes consistent with their role as potential biomarkers of disease...
- Pharmacogenetics and obesity: common gene variants influence weight loss response of the norepinephrine/dopamine transporter inhibitor GW320659 in obese subjectsColin F Spraggs
Genetics Research, GlaxoSmithKline Research and Development, Medicines Research Centre, Stevenage, UK
Pharmacogenet Genomics 15:883-9. 2005....
- Pharmacogenetics and pharmacogenomics: recent developments, their clinical relevance and some ethical, social, and legal implicationsPaul W Norbert
J Mol Med (Berl) 81:135-40. 2003..Finally, we provide a framework for the analysis of social accountability that can be used for technology development and technology assessment with regard to pharmacogenomics in particular and molecular medicine in general...
- SNPs--where's the beef?Allen D Roses
GlaxoSmithKline, Genetics Research, Research Triangle Park, NC 27709, USA
Pharmacogenomics J 2:277-83. 2002
- The knockout mouse projectChristopher P Austin
National Human Genome Research Institute, National Institutes of Health, Building 31, Room 4B09, 31 Center Drive, Bethesda, Maryland 20892, USA
Nat Genet 36:921-4. 2004..It is time to harness new technologies and efficiencies of production to mount a high-throughput international effort to produce and phenotype knockouts for all mouse genes, and place these resources into the public domain...
- Pharmacogenetics and drug development: the path to safer and more effective drugsAllen D Roses
Genetics Research, GlaxoSmithKline, Five Moore Drive, Research Triangle Park, North Carolina 27709, USA
Nat Rev Genet 5:645-56. 2004..The rapid identification of adverse events during and after drug development using genomic mapping tools is also reviewed...
- A single-nucleotide polymorphism tagging set for human drug metabolism and transportKourosh R Ahmadi
Department of Biology Galton Lab, University College London, The Darwin Building, Gower Street, London WC1E 6BT, UK
Nat Genet 37:84-9. 2005..The analyses also suggest that rare variation is not amenable to tagging strategies...
- Disease-specific target selection: a critical first step down the right roadAllen D Roses
GlaxoSmithKline R and D, Research Triangle Park, NC 27709, USA
Drug Discov Today 10:177-89. 2005..This review summarizes the methods and intensive data analyses leading to target gene identification for type 2 diabetes mellitus, including the statistical permutation methodology used to correct for many variables...