title: CACNA1C polymorphism and altered phosphorylation of tau in bipolar disorder.
abstract: Several genome-wide association studies and case-control studies have associated the single nucleotide polymorphism (SNP) rs1006737, situated in CACNA1C encoding the alpha 1C subunit of the L-type voltage-gated calcium channel, with bipolar disorder and other psychiatric disorders. However, the causal pathway linking genetic variants in CACNA1C with increased risk for developing brain disorders remains unclear. Here, we explored the association between the rs1006737 SNP and cerebrospinal fluid (CSF) markers. We found a significant association between the risk allele in rs1006737 and a decreased CSF hyperphosphorylated tau/total tau ratio in patients with bipolar disorder, thus linking variation in the CACNA1C gene to a neurochemical marker of neuroaxonal plasticity in those with this disorder.
authors.affiliation: Joel Jakobsson, PhD, Erik Pålsson, PhD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Carl Sellgren, PhD, MD, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Frida Rydberg, MD, Agneta Ekman, PhD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Henrik Zetterberg, PhD, MD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden and UCL Institute of Neurology, London, UK; Kaj Blennow, PhD, MD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Mikael Landén, PhD, MD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Department of Medical Epidemiology and Biostatistics, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden joel.jakobsson@neuro.gu.se.
authors.forename: Joel
authors.initials: J
authors.lastname: Jakobsson
authors.affiliation: Joel Jakobsson, PhD, Erik Pålsson, PhD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Carl Sellgren, PhD, MD, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Frida Rydberg, MD, Agneta Ekman, PhD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Henrik Zetterberg, PhD, MD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden and UCL Institute of Neurology, London, UK; Kaj Blennow, PhD, MD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Mikael Landén, PhD, MD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Department of Medical Epidemiology and Biostatistics, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Pålsson
authors.affiliation: Joel Jakobsson, PhD, Erik Pålsson, PhD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Carl Sellgren, PhD, MD, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Frida Rydberg, MD, Agneta Ekman, PhD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Henrik Zetterberg, PhD, MD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden and UCL Institute of Neurology, London, UK; Kaj Blennow, PhD, MD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Mikael Landén, PhD, MD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Department of Medical Epidemiology and Biostatistics, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Carl
authors.initials: C
authors.lastname: Sellgren
authors.affiliation: Joel Jakobsson, PhD, Erik Pålsson, PhD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Carl Sellgren, PhD, MD, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Frida Rydberg, MD, Agneta Ekman, PhD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Henrik Zetterberg, PhD, MD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden and UCL Institute of Neurology, London, UK; Kaj Blennow, PhD, MD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Mikael Landén, PhD, MD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Department of Medical Epidemiology and Biostatistics, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Frida
authors.initials: F
authors.lastname: Rydberg
authors.affiliation: Joel Jakobsson, PhD, Erik Pålsson, PhD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Carl Sellgren, PhD, MD, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Frida Rydberg, MD, Agneta Ekman, PhD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Henrik Zetterberg, PhD, MD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden and UCL Institute of Neurology, London, UK; Kaj Blennow, PhD, MD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Mikael Landén, PhD, MD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Department of Medical Epidemiology and Biostatistics, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Agneta
authors.initials: A
authors.lastname: Ekman
authors.affiliation: Joel Jakobsson, PhD, Erik Pålsson, PhD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Carl Sellgren, PhD, MD, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Frida Rydberg, MD, Agneta Ekman, PhD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Henrik Zetterberg, PhD, MD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden and UCL Institute of Neurology, London, UK; Kaj Blennow, PhD, MD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Mikael Landén, PhD, MD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Department of Medical Epidemiology and Biostatistics, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Joel Jakobsson, PhD, Erik Pålsson, PhD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Carl Sellgren, PhD, MD, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Frida Rydberg, MD, Agneta Ekman, PhD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Henrik Zetterberg, PhD, MD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden and UCL Institute of Neurology, London, UK; Kaj Blennow, PhD, MD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Mikael Landén, PhD, MD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Department of Medical Epidemiology and Biostatistics, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Joel Jakobsson, PhD, Erik Pålsson, PhD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Carl Sellgren, PhD, MD, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Frida Rydberg, MD, Agneta Ekman, PhD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Henrik Zetterberg, PhD, MD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden and UCL Institute of Neurology, London, UK; Kaj Blennow, PhD, MD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Mikael Landén, PhD, MD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Department of Medical Epidemiology and Biostatistics, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Landén
mesh_terms: D000328:Adult; D000483:Alleles; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001714:Bipolar Disorder / Q000235:genetics*; D020746:Calcium Channels, L-Type / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D020641:Polymorphism, Single Nucleotide; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D015415:Biomarkers; C079146:CACNA1C protein, human; D020746:Calcium Channels, L-Type; D016875:tau Proteins