Causal association between insulin sensitivity index and Alzheimer's disease

全基因组关联研究 孟德尔随机化 遗传关联 多效性 观察研究 遗传学 医学 生物 内科学 基因型 单核苷酸多态性 遗传变异 基因 表型
作者
Fang Xu,Shiyang Wu,Shan Gao,Xuan Li,Chen Huang,Yan Chen,Ping Zhu,Guiyou Liu
出处
期刊:Journal of Neurochemistry [Wiley]
标识
DOI:10.1111/jnc.16254
摘要

Abstract Evidence from observational and Mendelian randomization (MR) studies suggested that insulin resistance (IR) was associated with Alzheimer's disease (AD). However, the causal effects of different indicators of IR on AD remain inconsistent. Here, we aim to assess the causal association between the insulin sensitivity index (ISI), a measure of post‐prandial IR, and the risk of AD. We first conducted primary and secondary univariable MR analyses. We selected 8 independent genome‐wide significant ( p < 5E‐08, primary analyses) and 61 suggestive ( p < 1E‐05, secondary analyses) ISI genetic variants from large‐scale genome‐wide association studies (GWAS; N = 53 657), respectively, and extracted their corresponding GWAS summary statistics from AD GWAS, including IGAP2019 ( N = 63 926) and FinnGen_G6_AD_WIDE ( N = 412 181). We selected five univariable MR methods and used heterogeneity, horizontal pleiotropy test, and leave‐one‐out sensitivity analysis to confirm the stability of MR estimates. Finally, we conducted a meta‐analysis to combine MR estimates from two non‐overlapping AD GWAS datasets. We further performed multivariable MR (MVMR) to assess the potential mediating role of type 2 diabetes (T2D) on the association between ISI and AD using two MVMR methods. In univariable MR, utilizing 8 genetic variants in primary analyses, we found a significant causal association of genetically increased ISI with decreased risk of AD (OR = 0.79, 95% CI: 0.68–0.92, p = 0.003). Utilizing 61 genetic variants in secondary analyses, we found consistent findings of a causal effect of genetically increased ISI on the decreased risk of AD (OR = 0.89, 95% CI: 0.82–0.96, p = 0.003). Heterogeneity, horizontal pleiotropy test, and leave‐one‐out sensitivity analysis ensured the reliability of the MR estimates. In MVMR, we found no causal relationship between ISI and AD after adjusting for T2D ( p > 0.05). We provide genetic evidence that increased ISI is significantly and causally associated with reduced risk of AD, which is mediated by T2D. These findings may inform prevention strategies directed toward IR‐associated T2D and AD. image
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
认真写论文的小梁完成签到,获得积分10
2秒前
吾皇完成签到 ,获得积分10
3秒前
3秒前
李昕123发布了新的文献求助10
4秒前
等待蚂蚁发布了新的文献求助10
4秒前
ding应助weijie采纳,获得10
4秒前
mimi完成签到,获得积分10
5秒前
吃不饱星球球长应助tang采纳,获得50
7秒前
杨春天发布了新的文献求助10
7秒前
rrr发布了新的文献求助10
8秒前
9秒前
11秒前
LMFY完成签到 ,获得积分10
12秒前
轻松的纸鹤完成签到,获得积分10
13秒前
13秒前
13秒前
16秒前
123完成签到 ,获得积分10
16秒前
jisimyang98发布了新的文献求助10
17秒前
medxyy完成签到,获得积分10
18秒前
风趣的茹嫣完成签到 ,获得积分10
18秒前
20秒前
rrr完成签到,获得积分10
21秒前
无花果应助科研通管家采纳,获得10
22秒前
Akim应助科研通管家采纳,获得10
22秒前
爆米花应助科研通管家采纳,获得10
22秒前
22秒前
领导范儿应助科研通管家采纳,获得10
22秒前
大模型应助科研通管家采纳,获得10
22秒前
科研通AI2S应助科研通管家采纳,获得10
22秒前
在水一方应助科研通管家采纳,获得10
22秒前
小二郎应助科研通管家采纳,获得30
22秒前
大模型应助科研通管家采纳,获得10
22秒前
SciGPT应助科研通管家采纳,获得10
23秒前
不安青牛应助科研通管家采纳,获得10
23秒前
23秒前
不苦给不苦的求助进行了留言
23秒前
君莫笑完成签到 ,获得积分10
23秒前
鑫叶完成签到,获得积分10
24秒前
24秒前
高分求助中
Evolution 10000
юрские динозавры восточного забайкалья 800
English Wealden Fossils 700
Distribution Dependent Stochastic Differential Equations 500
A new species of Coccus (Homoptera: Coccoidea) from Malawi 500
A new species of Velataspis (Hemiptera Coccoidea Diaspididae) from tea in Assam 500
PraxisRatgeber: Mantiden: Faszinierende Lauerjäger 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3157989
求助须知:如何正确求助?哪些是违规求助? 2809366
关于积分的说明 7881582
捐赠科研通 2467822
什么是DOI,文献DOI怎么找? 1313728
科研通“疑难数据库(出版商)”最低求助积分说明 630522
版权声明 601943