Additive sex-specific influence of common non-synonymous DISC1 variants on amygdala, basal ganglia, and white cortical surface area in healthy young adults.

Mühle, Christiane; Kreczi, Jakob; Rhein, Cosima; Richter-Schmidinger, Tanja; Alexopoulos, Panagiotis; Doerfler, Arnd; Lenz, Bernd; Kornhuber, Johannes

doi:10.1007/s00429-016-1253-6

2017

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Title:: Additive sex-specific influence of common non-synonymous DISC1 variants on amygdala, basal ganglia, and white cortical surface area in healthy young adults.
Document type:: Article; Journal Article
Author(s):: Mühle, Christiane; Kreczi, Jakob; Rhein, Cosima; Richter-Schmidinger, Tanja; Alexopoulos, Panagiotis; Doerfler, Arnd; Lenz, Bernd; Kornhuber, Johannes
Abstract:: The disrupted-in-schizophrenia-1 (DISC1) gene is known for its role in the development of mental disorders. It is also involved in neurodevelopment, cognition, and memory. To investigate the association between DISC1 variants and brain morphology, we analyzed the influence of the three common non-synonymous polymorphisms in DISC1 on specific brain structures in healthy young adults. The volumes of brain regions were determined in 145 subjects by magnetic resonance imaging and automated analysis using FreeSurfer. Genotyping was performed by high resolution melting of amplified products. In an additive genetic model, rs6675281 (Leu607Phe), rs3738401 (Arg264Gln), and rs821616 (Ser704Cys) significantly explained the volume variance of the amygdala (p = 0.007) and the pallidum (p = 0.004). A higher cumulative portion of minor alleles was associated with larger volumes of the amygdala (p = 0.005), the pallidum (p = 0.001), the caudate (p = 0.024), and the putamen (p = 0.007). Sex-stratified analysis revealed a strong genetic effect of rs6675281 on putamen and pallidum in females but not in males and an opposite influence of rs3738401 on the white cortical surface in females compared to males. The strongest single association was found for rs821616 and the amygdala volume in male subjects (p < 0.001). No effect was detected for the nucleus accumbens. We report-to our knowledge-for the first time a significant and sex-specific influence of common DISC1 variants on volumes of the basal ganglia, the amygdala and on the cortical surface area. Our results demonstrate that the additive model of all three polymorphisms outperforms their single analysis.
Journal title abbreviation:: Brain Struct Funct
Year:: 2017
Journal volume:: 222
Journal issue:: 2
Pages contribution:: 881-894
Language:: eng
Fulltext / DOI:: doi:10.1007/s00429-016-1253-6
Pubmed ID:: http://view.ncbi.nlm.nih.gov/pubmed/27369464
Print-ISSN:: 1863-2653
TUM Institution:: Klinik und Poliklinik für Psychiatrie und Psychotherapie
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mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Departments Clinical Medicine Klinik und Poliklinik für Psychiatrie und Psychotherapie (Prof. Priller)2017

mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Departments