当前位置：
X-MOL 学术
›
Aging Cell
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
A genome-wide association study of the frailty index highlights brain pathways in ageing
Aging Cell ( IF 8.0 ) Pub Date : 2021-08-25 , DOI: 10.1111/acel.13459 Janice L Atkins 1 , Juulia Jylhävä 2 , Nancy L Pedersen 2, 3 , Patrik K Magnusson 2 , Yi Lu 2 , Yunzhang Wang 2 , Sara Hägg 2 , David Melzer 1, 4 , Dylan M Williams 2, 5 , Luke C Pilling 1, 4
Aging Cell ( IF 8.0 ) Pub Date : 2021-08-25 , DOI: 10.1111/acel.13459 Janice L Atkins 1 , Juulia Jylhävä 2 , Nancy L Pedersen 2, 3 , Patrik K Magnusson 2 , Yi Lu 2 , Yunzhang Wang 2 , Sara Hägg 2 , David Melzer 1, 4 , Dylan M Williams 2, 5 , Luke C Pilling 1, 4
Affiliation
|
Frailty is a common geriatric syndrome and strongly associated with disability, mortality and hospitalization. Frailty is commonly measured using the frailty index (FI), based on the accumulation of a number of health deficits during the life course. The mechanisms underlying FI are multifactorial and not well understood, but a genetic basis has been suggested with heritability estimates between 30 and 45%. Understanding the genetic determinants and biological mechanisms underpinning FI may help to delay or even prevent frailty. We performed a genome-wide association study (GWAS) meta-analysis of a frailty index in European descent UK Biobank participants (n = 164,610, 60–70 years) and Swedish TwinGene participants (n = 10,616, 41–87 years). FI calculation was based on 49 or 44 self-reported items on symptoms, disabilities and diagnosed diseases for UK Biobank and TwinGene, respectively. 14 loci were associated with the FI (p < 5*10−8). Many FI-associated loci have established associations with traits such as body mass index, cardiovascular disease, smoking, HLA proteins, depression and neuroticism; however, one appears to be novel. The estimated single nucleotide polymorphism (SNP) heritability of the FI was 11% (0.11, SE 0.005). In enrichment analysis, genes expressed in the frontal cortex and hippocampus were significantly downregulated (adjusted p < 0.05). We also used Mendelian randomization to identify modifiable traits and exposures that may affect frailty risk, with a higher educational attainment genetic risk score being associated with a lower degree of frailty. Risk of frailty is influenced by many genetic factors, including well-known disease risk factors and mental health, with particular emphasis on pathways in the brain.
中文翻译：
虚弱指数的全基因组关联研究强调了衰老过程中的大脑通路
虚弱是一种常见的老年综合症，与残疾、死亡和住院密切相关。衰弱通常使用衰弱指数（FI）来衡量，该指数基于生命过程中许多健康缺陷的累积。FI 的潜在机制是多因素的，目前尚不清楚，但已提出遗传基础，遗传力估计在 30% 至 45% 之间。了解支撑 FI 的遗传决定因素和生物机制可能有助于延缓甚至预防衰弱。我们对欧洲血统英国 Biobank 参与者（ n = 164,610，60-70 岁）和瑞典 TwinGene 参与者（n = 10,616，41-87 岁）的虚弱指数进行了全基因组关联研究 (GWAS) 荟萃分析。FI 计算分别基于 UK Biobank 和 TwinGene 的 49 项或 44 项关于症状、残疾和诊断疾病的自我报告项目。14 个基因座与 FI 相关（p < 5*10 -8）。许多 FI 相关位点已与体重指数、心血管疾病、吸烟、HLA 蛋白、抑郁症和神经质等特征建立关联；然而，其中一个似乎很新颖。FI 的估计单核苷酸多态性 (SNP) 遗传力为 11%（0.11，SE 0.005）。在富集分析中，额叶皮层和海马体中表达的基因显着下调（调整后p < 0.05）。我们还使用孟德尔随机化来识别可能影响衰弱风险的可改变特征和暴露，教育程度较高的遗传风险评分与较低的衰弱程度相关。虚弱风险受到许多遗传因素的影响，包括众所周知的疾病风险因素和心理健康，特别是大脑中的通路。
更新日期：2021-09-15
中文翻译：
虚弱指数的全基因组关联研究强调了衰老过程中的大脑通路
虚弱是一种常见的老年综合症，与残疾、死亡和住院密切相关。衰弱通常使用衰弱指数（FI）来衡量，该指数基于生命过程中许多健康缺陷的累积。FI 的潜在机制是多因素的，目前尚不清楚，但已提出遗传基础，遗传力估计在 30% 至 45% 之间。了解支撑 FI 的遗传决定因素和生物机制可能有助于延缓甚至预防衰弱。我们对欧洲血统英国 Biobank 参与者（ n = 164,610，60-70 岁）和瑞典 TwinGene 参与者（n = 10,616，41-87 岁）的虚弱指数进行了全基因组关联研究 (GWAS) 荟萃分析。FI 计算分别基于 UK Biobank 和 TwinGene 的 49 项或 44 项关于症状、残疾和诊断疾病的自我报告项目。14 个基因座与 FI 相关（p < 5*10 -8）。许多 FI 相关位点已与体重指数、心血管疾病、吸烟、HLA 蛋白、抑郁症和神经质等特征建立关联；然而，其中一个似乎很新颖。FI 的估计单核苷酸多态性 (SNP) 遗传力为 11%（0.11，SE 0.005）。在富集分析中，额叶皮层和海马体中表达的基因显着下调（调整后p < 0.05）。我们还使用孟德尔随机化来识别可能影响衰弱风险的可改变特征和暴露，教育程度较高的遗传风险评分与较低的衰弱程度相关。虚弱风险受到许多遗传因素的影响，包括众所周知的疾病风险因素和心理健康，特别是大脑中的通路。
京公网安备 11010802027423号