Dataset Information

Alzheimer's Disease and Rheumatoid Arthritis: A Mendelian Randomization Study.

ABSTRACT: Alzheimer's disease (AD) is the most common neurodegenerative disease. In recent years, multiple pathway analyses of AD genome-wide association studies (GWAS) have been conducted, and provided strong support for immune pathways in AD. Rheumatoid arthritis (RA) is a chronic autoimmune disease. It is reported that antirheumatic drugs had protective effect on dementia in RA patients. However, observational studies have reported a controversial inverse relationship between AD and RA. In addition, Mendelian randomization studies have also been performed to evaluate the association of RA with AD. However, these studies reported inconsistent association of RA with AD. Until now, it is still unclear that AD is a causally associated with RA. Here, we performed a Mendelian randomization study to investigate the causal association of AD with RA. We analyzed the large-scale AD GWAS dataset (74,046 individuals) and RA GWAS dataset (58,284 individuals) from the European descent. However, we did not identify any significant association of AD with RA using inverse-variance weighted meta-analysis (IVW), weighted median regression and MR-Egger regression.

SUBMITTER: Cai Q

PROVIDER: S-EPMC6143656 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Alzheimer's Disease and Rheumatoid Arthritis: A Mendelian Randomization Study.

Cai Qixuan Q Xin Zhuoyuan Z Zuo Lin L Li Fan F Liu Bin B

Frontiers in neuroscience 20180912

Alzheimer's disease (AD) is the most common neurodegenerative disease. In recent years, multiple pathway analyses of AD genome-wide association studies (GWAS) have been conducted, and provided strong support for immune pathways in AD. Rheumatoid arthritis (RA) is a chronic autoimmune disease. It is reported that antirheumatic drugs had protective effect on dementia in RA patients. However, observational studies have reported a controversial inverse relationship between AD and RA. In addition, Me ...[more]

PMID: 30258348

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Project description:Currently, the causal association between sleep disorders and rheumatoid arthritis (RA) has been poorly understood. In this two-sample Mendelian randomization (TSMR) study, we tried to explore whether sleep disorders are causally associated with RA. Seven sleep-related traits were chosen from the published Genome-Wide Association Study (GWAS): short sleep duration, frequent insomnia, any insomnia, sleep duration, getting up, morningness (early-to-bed/up habit), and snoring, 27, 53, 57, 57, 70, 274, and 42 individual single-nucleotide polymorphisms (SNPs) (P < 5 × 10-8) were obtained as instrumental variables (IVs) for these sleep-related traits. Outcome variables were obtained from a public GWAS study that included 14,361 cases and 43,923 European Ancestry controls. The causal relationship between sleep disturbances and RA risk were evaluated by a two-sample Mendelian randomization (MR) analysis using inverse variance weighted (IVW), MR-Egger regression, weighted median, and weight mode methods. MR-Egger Regression and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) were used to test for horizontal pleomorphism and outliers. There was no evidence of a link between RA and frequent insomnia (IVW, odds ratio (OR): 0.99; 95% interval (CI): 0.84-1.16; P = 0.858), any insomnia (IVW, OR: 1.09; 95% CI: 0.85-1.42; P = 0.489), sleep duration (IVW, OR: 0.65, 95% CI: 0.38-1.10, P = 0.269), getting up (IVW, OR: 0.56, 95% CI: 0.13-2.46, P = 0.442), morningness (IVW, OR: 2.59; 95% CI: 0.73-9.16; P = 0.142), or snoring (IVW, OR: 0.95; 95% CI: 0.68-1.33; P = 0.757). Short sleep duration (6h) had a causal effect on RA, as supported by IVW and weighted median (OR: 1.47, 95% CI: 1.12-1.94, P = 0.006; OR: 1.43, 95%CI:1.01-2.05, P = 0.047). Sensitivity analysis showed that the results were stable. Our findings imply that short sleep duration is causally linked to an increased risk of RA. Therefore, sleep length should be considered in disease models, and physicians should advise people to avoid short sleep duration practices to lower the risk of RA.

Project description:Stroke and Alzheimer's disease (AD) are common neurological diseases. Several exiting studies indicated that late onset-AD and ischemic stroke have shared genetic links. Different kinds of stroke have different mechanisms. However, it remains unclear whether there is a causal relationship between different types of strokes, including any stroke (AS), any ischemic stroke (AIS), large-artery atherosclerotic stroke (LAS), and cardio-embolic stroke (CES), and AD. Herein, we conducted several Mendelian randomization (MR) studies to explore genetically causal link of different kinds of strokes and AD. The results for inverse-variance weighted (IVW) meta-analysis (? = -0.039, OR = 0.9618, and P-value = 0.750) and weighted median regression (WMR) (? = -0.156, OR = 0.8556, and P-value = 0.274) demonstrated that AS is not causally associated with AD risk. The result of MR-Egger regression (? = -1.312, P-value = 0.098) and intercept term (P-value = 0.105) illustrated no pleiotropy in this MR study. According to the results for IVW (P-value = 0.305, ? = -0.103, and OR = 0.9021) and WMR (P-value = 0.487, ? = -0.092, and OR = 0.9121) in the MR study between AIS and AD, there is no causal association between AIS and AD risk. In addition, the MR-Egger regression (P-value = 0.290 and ? = -0.512) and intercept term (P-value = 0.387) showed no potential pleiotropy. LAS is not causally associated with AD risk according to the MR results (IVW: P-value = 0.568, ? = 0.037, and OR = 1.0377; WMR: P-value = 0.793, ? = -0.022, and OR = 0.9782). Additionally, the results of MR-Egger regression (P-value = 0.122 and ? = -1.220) and intercept term (P-value = 0.110) showed no potential pleiotropy. Our results [IVW: P-value = 0.245, ? = -0.064, and OR = 0.938; WMR: P-value = 0.331, ? = -0.057, and OR = 0.9446; MR-Egger: P-value = 0.673 and ? = -0.062, and intercept term (P-value = 0.985)] further demonstrated there is no causal link between CES and AD and no pleiotropy in this MR study. In conclusion, different types of stroke, including AS, AIS, LAS, and CES, would not be causally associated with AD risk.

Dataset Information

Alzheimer's Disease and Rheumatoid Arthritis: A Mendelian Randomization Study.

Publications

Alzheimer's Disease and Rheumatoid Arthritis: A Mendelian Randomization Study.

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