阿尔茨海默病与肌少症的孟德尔随机化研究

李瑞; 苏建培; 李瑾; 邓文君; 张亚洲

doi:10.12259/j.issn.2095-610X.S20240804

阿尔茨海默病与肌少症的孟德尔随机化研究

doi: 10.12259/j.issn.2095-610X.S20240804

1.
昆明市第二人民医院老年病科，云南昆明　650204
2.
昆明医科大学第一附属医院老年消化科，云南昆明　650032

基金项目: 昆明市卫生健康委员会卫生科研项目（2022-03-10-004）；昆明市卫生人才培养项目[2022-sw（后备）-52]

详细信息

作者简介:
李瑞（1994～），女，云南昭通人，医学硕士，住院医师，主要从事老年医学临床工作

通讯作者:
张亚洲，E-mail：15887117301@163.com

中图分类号: R493；R685
计量
- 文章访问数: 579
- HTML全文浏览量: 724
- PDF下载量: 27
- 被引次数: 0
出版历程
- 收稿日期: 2024-02-17
- 网络出版日期: 2024-07-06
- 刊出日期: 2024-08-05

A Mendelian Randomization Study on Alzheimer’ s Disease and Sarcopenia

1.
Dept. of Geriatrics，2nd People’s Hospital of Kunming，Kunming Yunnan 650204
2.
Dept. of Geriatric Gastroenterology，The 1st Affiliated Hospital of Kunming Medical University，Kunming Yunnan 650032，China

摘要

摘要: 目的探究阿尔茨海默病与肌少症之间的因果关系。方法基于公开的全基因组关联分析（genome-wide association analysis ，GWAS）数据库中阿尔茨海默病与肌少症的3种相关表型：四肢瘦体质量、步行速度、低握力，通过逆方差加权法、中位数加权法、MR-Egger回归等进行两样本孟德尔随机化分析，并进行了异质性检验和多效性分析等敏感性分析。结果两样本孟德尔随机化研究显示，阿尔茨海默病可能会增加四肢瘦体质量的减少的风险（β = 0.010，95%CI：0.001～0.018， P = 0.021）；同时，阿尔茨海默病可能会减慢步行速度（β = 0.009，95%CI：0.003～0.016，P = 0.005）。结论阿尔茨海默病可能导致肌少症发生风险增加。
- 孟德尔随机化 /
- 阿尔茨海默病 /
- 肌少症
Abstract: Objective To explore the causal relationship between Alzheimer’ s disease and sarcopenia. Methods This study is based on three related phenotypes of Alzheimer's disease and sarcopenia in the public genome-wide association analysis （GWAS） database, namely, appendicular lean mass, walking speed, and low grip strength. Two-sample Mendelian randomization analysis was conducted using inverse variance weighting method, median weighting method, MR-Egger regression, etc., and sensitivity analysis was performed, including heterogeneity testing and multiple effect analysis. Results The MR analyses demonstrated that Alzheimer’ s disease may increase the risk of reduced appendicular lean mass （β = 0.010 , 95% confidence interval （CI） = 0.001～0.018, P = 0.021）, while Alzheimer’ s disease was a significantly correlated with low walking speed （β = 0.009, 95% confidence interval （CI） = 0.003～0.016, P = 0.005）. Conclusion Alzheimer’ s disease may increases the risk of sarcopenia.
- Mendelian randomization /
- Alzheimer’ s disease /
- Sarcopenia

HTML全文

图 2 阿尔茨海默病与肌少症的漏斗图

A ：阿尔茨海默病与四肢瘦体质量的漏斗图；B：阿尔茨海默病与步行速度的漏斗图；C：阿尔茨海默病与低握力的漏斗图。

Figure 2. Funnel plots of Alzheimer’ s disease and sarcopenia

下载: 全尺寸图片幻灯片

图 1 阿尔茨海默病与和肌少症的孟德尔随机化分析森林图

Figure 1. MR forest plot for Alzheimer’ s disease and Sarcopenia

下载: 全尺寸图片幻灯片

表 1 阿尔茨海默病与肌少症的3种相关表型 GWAS 数据信息表

Table 1. GWAS data information on Alzheimer’s disease and sarcopenia related traits

表型	ID号	出版年份	SNPs	样本量（n）	研究人群
四肢瘦体质量	ebi-a-GCST90000025	2020	18071518	450243	欧洲人群
步行速度	ukb-b-4711	2018	9851867	459915	欧洲人群
低握力	ebi-a-GCST90007526	2021	9336415	256523	欧洲人群
阿尔茨海默病	ieu-b-2	2019	10528610	63926	欧洲人群

下载: 导出CSV

参考文献(32)

[1]	Cruz-Jentoft A J,Sayer A A. Sarcopenia[J]. Lancet (London,England),2019,393(10191):2636-2646. doi: 10.1016/S0140-6736(19)31138-9
[2]	Larsson L,Degens H,Li M,et al. Sarcopenia: Aging-related loss of muscle mass and function[J]. Physiological Reviews,2019,99(1):427-511. doi: 10.1152/physrev.00061.2017
[3]	Petermann-Rocha F,Balntzi V,Gray S R,et al. Global prevalence of sarcopenia and severe sarcopenia: A systematic review and meta-analysis[J]. Journal of Cachexia,Sarcopenia and Muscle,2022,13(1):86-99.
[4]	Cruz-Jentoft A J,Baeyens J P,Bauer J M,et al. Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People[J]. Age and Ageing,2010,39(4):412-423. doi: 10.1093/ageing/afq034
[5]	Wu X,Li X,Xu M,et al. Sarcopenia prevalence and associated factors among older Chinese population: Findings from the China Health and Retirement Longitudinal Study[J]. PloS One,2021,16(3):e0247617. doi: 10.1371/journal.pone.0247617
[6]	DeTure M A,Dickson D W. The neuropathological diagnosis of Alzheimer's disease[J]. Molecular Neurodegeneration,2019,14(1):32. doi: 10.1186/s13024-019-0333-5
[7]	Crous-Bou M,Minguill ó n C,Gramunt N,et al. Alzheimer's disease prevention: From risk factors to early intervention[J]. Alzheimer's Research & Therapy,2017,9(1):71.
[8]	Scheltens P,De Strooper B,Kivipelto M,et al. Alzheimer's disease[J]. Lancet (London,England),2021,397(10284):1577-1590. doi: 10.1016/S0140-6736(20)32205-4
[9]	Selkoe D J,Hardy J. The amyloid hypothesis of Alzheimer's disease at 25 years[J]. EMBO Molecular Medicine,2016,8(6):595-608. doi: 10.15252/emmm.201606210
[10]	Del Campo N,Payoux P,Djilali A,et al. Relationship of regional brain β-amyloid to gait speed[J]. Neurology,2016,86(1):36-43. doi: 10.1212/WNL.0000000000002235
[11]	Brisendine M H,Drake J C. Early-stage Alzheimer's disease: Are skeletal muscle and exercise the key? [J]. Journal of Applied Physiology (Bethesda,Md : 1985),2023,134(3): 515-520.
[12]	Chang K V,Hsu T H,Wu W T,et al. Association between sarcopenia and cognitive impairment: A systematic review and meta-analysis [J]. Journal of the American Medical Directors Association,2016,17(12): 1164. e1167-1164. e15.
[13]	Sugimoto T,Ono R,Murata S,et al. Prevalence and associated factors of sarcopenia in elderly subjects with amnestic mild cognitive impairment or Alzheimer disease[J]. Current Alzheimer Research,2016,13(6):718-726. doi: 10.2174/1567205013666160211124828
[14]	Davies N M,Holmes M V,Davey Smith G. Reading Mendelian randomisation studies: A guide,glossary,and checklist for clinicians[J]. BMJ (Clinical Research ed),2018,362:k601.
[15]	Jones G,Trajanoska K,Santanasto A J,et al. Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women[J]. Nature Communications,2021,12(1):654. doi: 10.1038/s41467-021-20918-w
[16]	Zillikens M C,Demissie S,Hsu Y H,et al. Large meta-analysis of genome-wide association studies identifies five loci for lean body mass[J]. Nature Communications,2017,8(1):80. doi: 10.1038/s41467-017-00031-7
[17]	Cawthon P M. Assessment of lean mass and physical performance in sarcopenia [J]. Journal of Clinical Densitometry : The Official Journal of the International Society for Clinical Densitometry,2015,18(4): 467-471.
[18]	Chen L K,Woo J,Assantachai P,et al. Asian Working Group for Sarcopenia: 2019 consensus update on sarcopenia diagnosis and treatment [J]. Journal of the American Medical Directors Association,2020,21(3): 300-307. e302.
[19]	Visser M,Fuerst T,Lang T,et al. Validity of fan-beam dual-energy X-ray absorptiometry for measuring fat-free mass and leg muscle mass. Health,Aging,and Body Composition Study-Dual-Energy X-ray Absorptiometry and Body Composition Working Group [J]. Journal of Applied Physiology (Bethesda,Md : 1985),1999,87(4): 1513-1520.
[20]	Pei Y F,Liu Y Z,Yang X L,et al. The genetic architecture of appendicular lean mass characterized by association analysis in the UK Biobank study[J]. Communications Biology,2020,3(1):608. doi: 10.1038/s42003-020-01334-0
[21]	Zhao Q,Chen Y,Wang J,et al. Powerful three-sample genome-wide design and robust statistical inference in summary-data Mendelian randomization[J]. International Journal of Epidemiology,2019,48(5):1478-1492. doi: 10.1093/ije/dyz142
[22]	Bowden J,Davey Smith G,Haycock PC,et al. Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator[J]. Genetic Epidemiology,2016,40(4):304-314. doi: 10.1002/gepi.21965
[23]	Bowden J,Davey Smith G,Burgess S. Mendelian randomization with invalid instruments: Effect estimation and bias detection through Egger regression[J]. International Journal of Epidemiology,2015,44(2):512-525. doi: 10.1093/ije/dyv080
[24]	Pierce B L,Ahsan H,Vanderweele T J. Power and instrument strength requirements for Mendelian randomization studies using multiple genetic variants[J]. International Journal of Epidemiology,2011,40(3):740-752. doi: 10.1093/ije/dyq151
[25]	Ogawa Y,Kaneko Y,Sato T,et al. Sarcopenia and muscle functions at various stages of Alzheimer disease[J]. Frontiers in Neurology,2018,9:710. doi: 10.3389/fneur.2018.00710
[26]	Takagi D,Hirano H,Watanabe Y,et al. Relationship between skeletal muscle mass and swallowing function in patients with Alzheimer's disease[J]. Geriatrics & Gerontology International,2017,17(3):402-409.
[27]	Kim J,Choi K H,Cho S G,et al. Association of muscle and visceral adipose tissues with the probability of Alzheimer's disease in healthy subjects[J]. Scientific Reports,2019,9(1):949. doi: 10.1038/s41598-018-37244-9
[28]	He P,Zhou C,Ye Z,et al. Walking pace,handgrip strength,age,APOE genotypes,and new-onset dementia: The UK Biobank prospective cohort study[J]. Alzheimer's Research & Therapy,2023,15(1):9.
[29]	Manini T M,Hong S L,Clark B C. Aging and muscle: A neuron's perspective[J]. Current Opinion in Clinical Nutrition and Metabolic Care,2013,16(1):21-26. doi: 10.1097/MCO.0b013e32835b5880
[30]	Pan JX,Lee D,Sun D,et al. Muscular Swedish mutant APP-to-Brain axis in the development of Alzheimer's disease[J]. Cell Death & Disease,2022,13(11):952.
[31]	Xu H,Bhaskaran S,Piekarz K M,et al. Age related changes in muscle mass and force generation in the triple transgenic (3xTgAD) mouse model of Alzheimer's disease[J]. Frontiers in Aging Neuroscience,2022,14:876816. doi: 10.3389/fnagi.2022.876816
[32]	Seo J S,Leem Y H,Lee K W,et al. Severe motor neuron degeneration in the spinal cord of the Tg2576 mouse model of Alzheimer disease [J]. Journal of Alzheimer's Disease : JAD,2010,21(1): 263-276.

相关文章(20)

[1]	刘慧, 严国纪, 吴嘉, 王丹, 习杨彦彬, 李珊珊. 血栓通对阿尔茨海默症模型小鼠认知功能及神经异常兴奋性的作用及其机制研究, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20240204
[2]	王亚敏, 李媛媛, 薛艳云. 基于脑血流动力学、炎性因子探究银杏叶注射液联合多奈哌齐治疗阿尔茨海默病的临床疗效, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20240524
[3]	张苏, 黄正, 李娜, 许静, 陶怡婷. 坚果摄入量与慢性阻塞性肺疾病的两样本孟德尔随机化研究, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20241112
[4]	郭学云, 李娜, 陶国仲, 黄正. 油性坚果摄入量与原发性肺癌的两样本孟德尔随机化研究, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20240606
[5]	梁碧娟, 李华, 王志敏, 顾俊, 杨磊, 苏建培. 营养干预联合抗阻运动对老年肌少症的影响, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20230613
[6]	何慧萍, 何尧苇, 沈宗霖, 宋肖肖, 李葆罗, 姜红燕. 阿尔茨海默病与轻度认知功能障碍患者精神行为症状比较分析, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20220913
[7]	宿玮洁, 张美沙, 李佳凝, 刘颖, 徐丁洁, 常宏. Ang Ⅱ诱导大鼠成肌细胞萎缩模型的构建, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20211026
[8]	马菊香, 马永红, 高姗姗, 吴珏, 朱珉, 段振玲. 静脉超声造影对子宫腺肌症和子宫肌瘤的鉴别诊断价值, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20201109
[9]	郭玉倩, 曾跃勤, 吴超, 陆姜利, 杨艺, 郑红, 梁张. Aβ_25-35联合D-半乳糖诱导树鼩AD模型的建立, 昆明医科大学学报.
[10]	檀雅欣, 李珊, 王廷华, 习杨彦彬. APP/PS1+SCN2B-/-转基因小鼠模型的建立及鉴定, 昆明医科大学学报.
[11]	龚霞蓉, 芮茂萍, 毕国力, 郭家智, 陈婧, 符浩, 边立功, 吴昆华. 线粒体脑肌病合并乳酸血症和卒中样发作的影像学表现, 昆明医科大学学报.
[12]	邓苙, 李劲涛, 曹光琼. NGF-BMSCs移植对阿尔茨海默病大鼠神经行为学的改善, 昆明医科大学学报.
[13]	黄微. 阿尔茨海默病的 Hcy、 CRP变化与精神行为相关性临床观察, 昆明医科大学学报.
[14]	黄微. 以睡眠障碍为首要表现的阿尔茨海默病患者的临床观察, 昆明医科大学学报.
[15]	李源. 人参皂苷Rg1对AD大鼠脑片模型Bcl-2表达的影响, 昆明医科大学学报.
[16]	凌大庆. 高同型半胱氨酸血症骨骼肌TRB3表达与糖代谢的关系, 昆明医科大学学报.
[17]	王宇刚. 龟芪生精胶囊治疗男性少弱精子症临床观察, 昆明医科大学学报.
[18]	胡东辉. 阿立哌唑与利培酮治疗阿尔茨海默病性痴呆精神症状的临床对照, 昆明医科大学学报.
[19]	廖红云. 子宫动脉栓塞术治疗子宫腺肌症的临床疗效, 昆明医科大学学报.
[20]	. 前列地尔联合银杏达莫、盐酸丁咯地尔治疗突发性耳聋58例分析, 昆明医科大学学报.