title: Genetic, psychosocial and clinical factors associated with hippocampal volume in the general population.
abstract: The hippocampus--crucial for memory formation, recall and mood regulation--is involved in the pathophysiology of dementia and depressive disorders. Recent genome-wide association studies (GWAS) have identified five genetic loci associated with hippocampal volume (HV). Previous studies have described psychosocial and clinical factors (for example, smoking, type 2 diabetes and hypertension) to have an impact on HV. However, the interplay between genetic, psychosocial and clinical factors on the HV remains unclear. Still, it is likely that genetic variants and clinical or psychosocial factors jointly act in modifying HV; it might be possible they even interact. Knowledge of these factors might help to quantify ones individual risk of or rather resilience against HV loss. We investigated subjects (N=2463; 55.7% women; mean age 53 years) from the Study of Health in Pomerania (SHIP-2; SHIP-TREND-0) who underwent whole-body magnetic resonance imaging (MRI) and genotyping. HVs were estimated with FreeSurfer. For optimal nonlinear model fitting, we used regression analyses with restricted cubic splines. Genetic variants and associated psychosocial or clinical factors were jointly assessed for potential two-way interactions. We observed associations between HV and gender (P<0.0001), age (P<0.0001), body height (P<0.0001), education (P=0.0053), smoking (P=0.0058), diastolic blood pressure (P=0.0211), rs7294919 (P=0.0065), rs17178006 (P=0.0002), rs6581612 (P=0.0036), rs6741949 (P=0.0112) and rs7852872 (P=0.0451). In addition, we found three significant interactions: between rs7294919 and smoking (P=0.0473), rs7294919 and diastolic blood pressure (P=0.0447) and between rs7852872 and rs6581612 (P=0.0114). We suggest that these factors might have a role in the individual susceptibility to hippocampus-associated disorders.
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
authors.forename: D
authors.identifier: 0000000343249298
authors.initials: D
authors.lastname: Janowitz
authors.affiliation: Department of Prosthetic Dentistry, Gerostomatology and Dental Materials, Center of Oral Health, University Medicine Greifswald, Greifswald, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Schwahn
authors.affiliation: 1] Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany [2] German Center for Neurodegenerative Diseases DZNE, Site Rostock/ Greifswald, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Borchardt
authors.affiliation: German Center for Neurodegenerative Diseases DZNE, Site Rostock/ Greifswald, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Wittfeld
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Schulz
authors.affiliation: Institute of Clinical Psychology, University of Heidelberg, Heidelberg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Barnow
authors.affiliation: Department of Prosthetic Dentistry, Gerostomatology and Dental Materials, Center of Oral Health, University Medicine Greifswald, Greifswald, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Biffar
authors.affiliation: 1] German Center for Neurodegenerative Diseases DZNE, Site Rostock/ Greifswald, Germany [2] Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Hoffmann
authors.affiliation: 1] Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany [2] Section of Biomedical Image Analysis, Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: M
authors.identifier: 0000000194475805
authors.initials: M
authors.lastname: Habes
authors.affiliation: Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Homuth
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Nauck
authors.affiliation: Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Hegenscheid
authors.affiliation: Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Lotze
authors.affiliation: Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Völzke
authors.affiliation: 1] Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany [2] Department of Psychiatry and Psychotherapy, HELIOS Hospital Stralsund, Stralsund, Germany.
authors.forename: H J
authors.initials: HJ
authors.lastname: Freyberger
authors.affiliation: 1] Department of Neurology, Boston University School of Medicine, Boston, MA, USA [2] Institut National de la Santé et de la Recherche Médicale (INSERM), U740, Paris, France [3] University of Paris 7 Denis-Diderot, Paris, France [4] Department of Neurology, Lariboisière Hospital, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Debette
authors.affiliation: 1] Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany [2] German Center for Neurodegenerative Diseases DZNE, Site Rostock/ Greifswald, Germany [3] Department of Psychiatry and Psychotherapy, HELIOS Hospital Stralsund, Stralsund, Germany.
authors.forename: H J
authors.initials: HJ
authors.lastname: Grabe
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001794:Blood Pressure; D001827:Body Height; D015897:Comorbidity; D003866:Depressive Disorder / Q000453:epidemiology; D004522:Educational Status; D005260:Female; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006624:Hippocampus / Q000033:anatomy & histology* / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D012737:Sex Factors; D012907:Smoking / Q000453:epidemiology; D012959:Socioeconomic Factors; D055815:Young Adult