Premium
P2‐130: BACKGROUND GENETICS IMPACTS MICROSTRUCTURE MEASURES IN MOTOR CORTEX AND HIPPOCAMPUS OF WILDTYPE AND 5XFAD MICE
Author(s) -
Grudny Matteo,
Neuner Sarah M.,
Dunn Amy R.,
Pompilus Marjory,
Kaczorowski Catherine C.,
Febo Marcelo
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.06.2537
Subject(s) - neuroscience , presenilin , diffusion mri , hippocampus , hippocampal formation , white matter , psychology , neuroimaging , biology , alzheimer's disease , pathology , medicine , disease , magnetic resonance imaging , radiology
(n1⁄4949). Controls were defined as AD with no dysphoria. GWAS was conducted in PLINK and meta-analysed using METAL in a fixed effect model. MDD polygenic risk scores were generated at 10 thresholds (PT) ranging from p1⁄453 10 8 to 1 using PRSice. Logistic regression was used to calculate association for each cohort and meta-analysed utilizing a random effects model in R. We carried out a further MDD PRS analysis on AD with previous MDD history (n1⁄4444) versus no history. Results: No variants exceeded genome-wide significance in either phenotype. MDD PRS was significantly associated with both any dysphoria and severe dysphoria at an optimum PT of 0.5. The variance explained for both phenotypes was <0.1%. The strongest association was for severe dysphoria [odds ratio (OR) 1.2; 95% confidence interval (CI): 1.1-1.3, p1⁄40.004]. For AD with previous MDD the optimum PT was at 1.0 (OR 1.2; 95% CI: 1.0-1.3, p1⁄40.008). Conclusions: In this first GWAS, we found no genome-wide significant findings likely due to the study being underpowered. PRS data suggest that AD with dysphoria and MDD share some polygenic structure, however the contribution of MDD PRS appears to be small. These results are hypothesis generating and more research into the link between AD with dysphoria and MDD is warranted.