Unlocking the causal link of metabolically different adiposity subtypes with brain volumes and the risks of dementia and stroke: a Mendelian randomization study
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2021
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Mulugeta, A.
Lumsden, A.
Hyppönen, E.
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Journal article
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Neurobiology of Aging, 2021; 102:161-169
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Abstract
To establish causal evidence for the association of adiposity-related metabolic abnormalities with brain volumes, and the risks of dementia and stroke, we applied 1- and 2-sample Mendelian randomization (MR) analyses using up to 336,309 UK Biobank participants. We used 3 classes of genetic instruments, which all increase body mass index but are associated with different metabolic profiles (unfavorable, neutral and favorable). We validated the instruments using anthropometric and cardio-metabolic traits. Both metabolically unfavorable and metabolically neutral adiposity associated with lower gray matter volume (GMV, −9.28 cm3, −12.90 to −5.66 and −12.02 cm3, −20.07 to −3.97, respectively). Metabolically favorable adiposity was tentatively associated with a higher GMV (16.21 cm3, −0.21 to 32.68). No causal evidence was seen for white matter and hippocampal volume, and volume of white matter hyperintensities, or with the risks of dementia and stroke (all p > 0.60). These findings suggest that obesity-related metabolic abnormalities may contribute to GMV atrophy, warranting further studies.
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Data source: Supplementary materials, https://doi.org/10.1016/j.neurobiolaging.2021.02.010
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Copyright 2021 Elsevier
Access Condition Notes: Accepted manuscript available after 1 January 2022