Australian Centre for Precision Health, Unit of Clinical and Health Sciences, University of South Australia, Adelaide, Australia; Department of Pharmacology and Clinical Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; South Australian Health and Medical Research Institute, Adelaide, Australia.
Australian Centre for Precision Health, Unit of Clinical and Health Sciences, University of South Australia, Adelaide, Australia; South Australian Health and Medical Research Institute, Adelaide, Australia.
Neurobiol Aging. 2021 Jun;102:161-169. doi: 10.1016/j.neurobiolaging.2021.02.010. Epub 2021 Feb 21.
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 cm, -12.90 to -5.66 and -12.02 cm, -20.07 to -3.97, respectively). Metabolically favorable adiposity was tentatively associated with a higher GMV (16.21 cm, -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.
为了确定肥胖相关代谢异常与脑容量之间的因果关系证据，以及痴呆症和中风的风险，我们使用了 1 样本和 2 样本 Mendelian 随机分析，使用了多达 336309 名英国生物库参与者的数据。我们使用了 3 类遗传工具，这些工具都增加了体重指数，但与不同的代谢特征相关（不利、中性和有利）。我们使用人体测量和心血管代谢特征来验证这些工具。代谢不良和代谢中性的肥胖都与灰质体积降低有关（-9.28cm，-12.90 到-5.66 和-12.02cm，-20.07 到-3.97）。代谢有利的肥胖与较高的灰质体积有关（16.21cm，0.21 到 32.68）。对于白质和海马体体积，以及白质高信号体积和痴呆症和中风的风险，没有因果关系的证据（均 p>0.60）。这些发现表明，肥胖相关的代谢异常可能导致灰质体积萎缩，值得进一步研究。
