@article{LiStomaLottaetal.2020,
  author    = {Li, Chen and Stoma, Svetlana and Lotta, Luca A. and Warner, Sophie and Albrecht, Eva and Allione, Alessandra and Arp, Pascal P. and Broer, Linda and Buxton, Jessica L. and Boeing, Heiner and Langenberg, Claudia and Codd, Veryan},
  title     = {Genome-wide association analysis in humans links nucleotide metabolism to leukocyte telomere length},
  series = {American Journal of Human Genetics},
  volume    = {106},
  journal   = {American Journal of Human Genetics},
  number    = {3},
  publisher = {Elsevier},
  address   = {Amsterdam},
  pages     = {16},
  year      = {2020},
  abstract  = {Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1 , PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.},
  language  = {en}
}
@misc{LiStomaLottaetal.2020,
  author    = {Li, Chen and Stoma, Svetlana and Lotta, Luca A. and Warner, Sophie and Albrecht, Eva and Allione, Alessandra and Arp, Pascal P. and Broer, Linda and Buxton, Jessica L. and Boeing, Heiner and Langenberg, Claudia and Codd, Veryan},
  title     = {Genome-wide association analysis in humans links nucleotide metabolism to leukocyte telomere length},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {3},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-52684},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-526843},
  pages     = {18},
  year      = {2020},
  abstract  = {Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1 , PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.},
  language  = {en}
}
@article{KumarGoodwinUhouseetal.2015,
  author    = {Kumar, Kevin K. and Goodwin, Cody R. and Uhouse, Michael A. and Bornhorst, Julia and Schwerdtle, Tanja and Aschner, Michael A. and McLean, John A. and Bowman, Aaron B.},
  title     = {Untargeted metabolic profiling identifies interactions between Huntington's disease and neuronal manganese status},
  series = {Metallomics},
  volume    = {7},
  journal   = {Metallomics},
  publisher = {RSC Publ.},
  address   = {Cambridge},
  issn      = {1756-591X},
  doi       = {10.1039/C4MT00223G},
  pages     = {363 -- 370},
  year      = {2015},
  abstract  = {Manganese (Mn) is an essential micronutrient for development and function of the nervous system. Deficiencies in Mn transport have been implicated in the pathogenesis of Huntington's disease (HD), an autosomal dominant neurodegenerative disorder characterized by loss of medium spiny neurons of the striatum. Brain Mn levels are highest in striatum and other basal ganglia structures, the most sensitive brain regions to Mn neurotoxicity. Mouse models of HD exhibit decreased striatal Mn accumulation and HD striatal neuron models are resistant to Mn cytotoxicity. We hypothesized that the observed modulation of Mn cellular transport is associated with compensatory metabolic responses to HD pathology. Here we use an untargeted metabolomics approach by performing ultraperformance liquid chromatography-ion mobility-mass spectrometry (UPLC-IM-MS) on control and HD immortalized mouse striatal neurons to identify metabolic disruptions under three Mn exposure conditions, low (vehicle), moderate (non-cytotoxic) and high (cytotoxic). Our analysis revealed lower metabolite levels of pantothenic acid, and glutathione (GSH) in HD striatal cells relative to control cells. HD striatal cells also exhibited lower abundance and impaired induction of isobutyryl carnitine in response to increasing Mn exposure. In addition, we observed induction of metabolites in the pentose shunt pathway in HD striatal cells after high Mn exposure. These findings provide metabolic evidence of an interaction between the HD genotype and biologically relevant levels of Mn in a striatal cell model with known HD by Mn exposure interactions. The metabolic phenotypes detected support existing hypotheses that changes in energetic processes underlie the pathobiology of both HD and Mn neurotoxicity.},
  language  = {en}
}
@misc{KumarGoodwinUhouseetal.2015,
  author    = {Kumar, Kevin K. and Goodwin, Cody R. and Uhouse, Michael A. and Bornhorst, Julia and Schwerdtle, Tanja and Aschner, Michael A. and McLean, John A. and Bowman, Aaron B.},
  title     = {Untargeted metabolic profiling identifies interactions between Huntington's disease and neuronal manganese status},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-94314},
  pages     = {363 -- 370},
  year      = {2015},
  abstract  = {Manganese (Mn) is an essential micronutrient for development and function of the nervous system. Deficiencies in Mn transport have been implicated in the pathogenesis of Huntington's disease (HD), an autosomal dominant neurodegenerative disorder characterized by loss of medium spiny neurons of the striatum. Brain Mn levels are highest in striatum and other basal ganglia structures, the most sensitive brain regions to Mn neurotoxicity. Mouse models of HD exhibit decreased striatal Mn accumulation and HD striatal neuron models are resistant to Mn cytotoxicity. We hypothesized that the observed modulation of Mn cellular transport is associated with compensatory metabolic responses to HD pathology. Here we use an untargeted metabolomics approach by performing ultraperformance liquid chromatography-ion mobility-mass spectrometry (UPLC-IM-MS) on control and HD immortalized mouse striatal neurons to identify metabolic disruptions under three Mn exposure conditions, low (vehicle), moderate (non-cytotoxic) and high (cytotoxic). Our analysis revealed lower metabolite levels of pantothenic acid, and glutathione (GSH) in HD striatal cells relative to control cells. HD striatal cells also exhibited lower abundance and impaired induction of isobutyryl carnitine in response to increasing Mn exposure. In addition, we observed induction of metabolites in the pentose shunt pathway in HD striatal cells after high Mn exposure. These findings provide metabolic evidence of an interaction between the HD genotype and biologically relevant levels of Mn in a striatal cell model with known HD by Mn exposure interactions. The metabolic phenotypes detected support existing hypotheses that changes in energetic processes underlie the pathobiology of both HD and Mn neurotoxicity.},
  language  = {en}
}