| 1. |
- Khalili, Bita, et al.
(författare)
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Associations between common genetic variants and income provide insights about the socioeconomic health gradient
- 2024
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We conducted a genome-wide association study (GWAS) on income among individuals of European descent and leveraged the results to investigate the socio-economic health gradient (N=668,288). We found 162 genomic loci associated with a common genetic factor underlying various income measures, all with small effect sizes. Our GWAS-derived polygenic index captures 1 - 4% of income variance, with only one-fourth attributed to direct genetic effects. A phenome-wide association study using this polygenic index showed reduced risks for a broad spectrum of diseases, including hypertension, obesity, type 2 diabetes, coronary atherosclerosis, depression, asthma, and back pain. The income factor showed a substantial genetic correlation (0.92, s.e. = .006) with educational attainment (EA). Accounting for EA's genetic overlap with income revealed that the remaining genetic signal for higher income related to better mental health but reduced physical health benefits and increased participation in risky behaviours such as drinking and smoking.
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| 2. |
- van der Velpen, Isabelle F., et al.
(författare)
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Psychosocial health modifies associations between HPA-axis function and brain structure in older age
- 2023
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Ingår i: Psychoneuroendocrinology. - : Elsevier. - 0306-4530 .- 1873-3360. ; 153
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dysregulation of the negative feedback loop of the hypothalamic-pituitary-adrenal (HPA) axis may have damaging effects on the brain, potentially under influence of psychosocial health factors. We studied associations between functioning of the negative feedback loop of HPA-axis, measured with a very low-dose dexamethasone suppression test (DST), and brain structure in middle-aged and older adults, and whether these associations were modified by psychosocial health.Methods: From 2006 to 2008, 1259 participants (mean age 57.6 +/- 6.4, 59.6 % female) of the population-based Rotterdam Study completed a very low-dose DST (0.25 mg) and underwent magnetic resonance imaging (MRI) of the brain. Self-reported psychosocial health (depressive symptoms, loneliness, marital status, perceived social support) were assessed in the same time period. Multivariable linear and logistic regression were used to study cross-sectional associations between cortisol response and brain volumetrics, cerebral small vessel disease markers and white matter structural integrity. To assess the effect of psychosocial health on these associations, analyses were further stratified for psychosocial health markers.Results: Cortisol response was not associated with markers of global brain structure in the overall study sample. However, in participants with clinically relevant depressive symptoms, a diminished cortisol response was associated with smaller white matter volume (mean difference: - 1.00 mL, 95 %CI = - 1.89;- 0.10) and smaller white matter hyperintensity volume (mean difference: - 0.03 mL (log), 95 %CI = - 0.05;0.00). In participants with low/moderate perceived social support compared to those with high social support, a diminished cortisol response was associated with larger gray matter volume (mean difference: 0.70 mL, 95 %CI = 0.01;1.39) and higher fractional anisotropy (standardized mean difference 0.03, 95 %CI = 0.00;0.06).Conclusion: Diminished function of the HPA-axis is differently associated with brain structure in communitydwelling middle-aged and older adults with clinically relevant depressive symptoms or suboptimal social support, but not in adults without depressive symptoms or with optimal social support.
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| 3. |
- Özel, Faith, et al.
(författare)
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Associations of neuroimaging markers with depressive symptoms over time in middle-aged and elderly persons
- 2023
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Ingår i: Psychological Medicine. - : Cambridge University Press. - 0033-2917 .- 1469-8978. ; 53:10, s. 4355-4363
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Tidskriftsartikel (refereegranskat)abstract
- Background Cerebrovascular disease is regarded as a potential cause of late-life depression. Yet, evidence for associations of neuroimaging markers of vascular brain disease with depressive symptoms is inconclusive. We examined the associations of neuroimaging markers and depressive symptoms in a large population-based study of middle-aged and elderly persons over time.Methods A total of 4943 participants (mean age = 64.6 +/- 11.1 years, 55.7% women) from the Rotterdam Study were included. At baseline, total brain volume, gray matter volume, white matter volume, white matter hyperintensities volume, cortical infarcts, lacunar infarcts, microbleeds, white matter fractional anisotropy, and mean diffusivity (MD) were measured with a brain MRI (1.5T). Depressive symptoms were assessed twice with the Center for Epidemiologic Studies Depression scale (median follow-up time: 5.5 years, IQR = 0.9). To assess temporal associations of neuroimaging markers and depressive symptoms, linear mixed models were used.Results A smaller total brain volume (beta = -0.107, 95% CI -0.192 to -0.022), larger white matter hyperintensities volume (beta = 0.047, 95% CI 0.010-0.084), presence of cortical infarcts (beta = 0.194, 95% CI 0.047-0.341), and higher MD levels (beta = 0.060, 95% CI 0.022-0.098) were cross-sectionally associated with more depressive symptoms. Longitudinal analyses showed that small total brain volume (beta = -0.091, 95% CI -0.167 to -0.015) and presence of cortical infarcts (beta = 0.168, 95% CI 0.022-0.314) were associated with increasing depressive symptoms over time. After stratification on age, effect sizes were more pronounced at older ages.Conclusions Neuroimaging markers of white matter microstructural damage were associated with depressive symptoms longitudinally in this study of middle-aged and elderly persons. These associations were more pronounced at older ages, providing evidence for the role of white matter structure in late-life depressive symptomatology.
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