Browsing by Author "Glymour, M. Maria"

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    Alzheimer's disease genetic risk variants beyond APOE ε4 predict mortality
    (Elsevier, 2017-08-24) Mez, Jesse; Marden, Jessica R.; Mukherjee, Shubhabrata; Walter, Stefan; Gibbons, Laura E.; Gross, Alden L.; Zahodne, Laura B.; Gilsanz, Paola; Brewster, Paul; Nho, Kwangsik; Crane, Paul K.; Larson, Eric B.; Glymour, M. Maria; Radiology and Imaging Sciences, School of Medicine
    • A genetic risk score from 21 non-APOE late-onset Alzheimer's disease risk variants predicts mortality. • The genetic risk score likely confers risk for mortality through its effect on dementia incidence. • Late-onset Alzheimer's disease risk loci effect estimates from genome-wide association unlikely suffer from selection bias.
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    Gene-based GWAS and -biological pathway analysis of the resilience of executive functioning
    (Springer US, 2014-03) Mukherjee, Shubhabrata; Kim, Sungeun; Ramanan, Vijay K.; Gibbons, Laura E.; Nho, Kwangsik; Glymour, M. Maria; Ertekin-Taner, Nilüfer; Montine, Thomas J.; Saykin, Andrew J.; Crane, Paul K.; Alzheimer’s Disease Neuroimaging Initiative; Department of Radiology and Imaging Sciences, School of Medicine
    Resilience in executive functioning (EF) is characterized by high EF measured by neuropsychological test performance despite structural brain damage from neurodegenerative conditions. We previously reported single nucleotide polymorphism (SNP) genome-wide association study (GWAS) results for EF resilience. Here, we report gene- and pathway-based analyses of the same resilience phenotype, using an optimal SNP-set (Sequence) Kernel Association Test (SKAT) for gene-based analyses (conservative threshold for genome-wide significance = 0.05/18,123=2.8×10−6) and the gene-set enrichment package GSA-SNP for biological pathway analyses (False discovery rate (FDR) < 0.05). Gene-based analyses found a genome-wide significant association between RNASE13 and EF resilience (p=1.33×10−7). Genetic pathways involved with dendritic/neuron spine, presynaptic membrane, postsynaptic density etc. were enriched with association to EF resilience. Although replication of these results is necessary, our findings indicate the potential value of gene- and pathway-based analyses in research on determinants of cognitive resilience.
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    Initiation of antidepressant medication and risk of incident stroke: using the Adult Changes in Thought cohort to address time-varying confounding
    (Elsevier, 2019-07) Glymour, M. Maria; Gibbons, Laura E.; Gilsanz, Paola; Gross, Alden L.; Mez, Jesse; Brewster, Paul W.; Marden, Jessica; Zahodne, Laura B.; Nho, Kwangsik; Hamilton, Jamie; Li, Gail; Larson, Eric B.; Crane, Paul K.; Radiology and Imaging Sciences, School of Medicine
    Purpose Depression strongly predicts stroke incidence, suggesting that treating depression may reduce stroke risk. Antidepressant medications, however, may increase stroke risk via direct pathways. Previous evidence on antidepressant medication and stroke incidence is mixed. We evaluated associations between antidepressant use and incident stroke. Methods For 2302 Adult Changes in Thought cohort participants with no stroke at study entry, we characterized antidepressant use from pharmacy records, biennial depressive symptoms with a 10-item Centers for Epidemiologic Study–Depression scale, and incident strokes from ICD codes. We used discrete-time survival models with inverse probability weighting to compare stroke risk associated with filling antidepressant prescriptions and by medication category: tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors, or other. Results Over an average 8.4-year follow-up, 441 incident strokes occurred. Filling antidepressant medications 3+ times versus 0–2 times predicted 35% increased odds of stroke (OR = 1.35; 95% CI: 0.98, 1.66). Use of TCAs was associated with stroke onset (OR per 10 fills = 1.28; CI: 1.04, 1.57), but use of selective serotonin reuptake inhibitors (OR = 0.98; CI: 0.80, 1.20) or other antidepressants (OR = 0.99; CI: 0.67, 1.45) was not. Conclusions Although patients who received antidepressant medication were at higher risk of stroke, this association appeared specific to TCA prescriptions.