Research Information System University of Greifswald

Janowitz D*¹, Schwahn C², Borchardt U¹, Wittfeld K³, Schulz A¹, Barnow S, Biffar R², Hoffmann W^3,4, Habes M⁴, Homuth G⁵, Nauck M⁶, Hegenscheid K⁷, Lotze M⁷, Völzke H⁸, Freyberger H¹, Debette S, Grabe H^1,3

1 - Klinik und Poliklinik für Psychiatrie und Psychotherapie

2 - Zentrum für Zahn-, Mund- und Kieferheilkunde

3 - Deutsches Zentrum für Neurodegenerative Erkrankungen Rostock / Greifswald Teilstandort Greifswald

4 - Institut für Community Medicine / Abt. Versorgungsepidemiologie und Community Health

5 - Interfakultäres Institut für Genetik und Funktionelle Genomforschung / Abt. Funktionelle Genomforschung

6 - Institut für Klinische Chemie und Laboratoriumsmedizin

7 - Zentrum für Radiologie / Institut für Diagnostische Radiologie und Neuroradiologie

8 - Institut für Community Medicine / Abt. SHIP KEF

Zentrum für Zahn-, Mund- und Kieferheilkunde / Poliklinik für Zahnärztliche Prothetik, Alterszahnheilkunde und Medizinische Werkstoffkunde

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.