Mendelian Randomization
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2021 ◽  
Vol 51 ◽  
pp. e210
Author(s):  
Ryan Arathimos ◽  
Amy Ronaldson ◽  
Laurence Howe ◽  
Chiara Fabbri ◽  
Saskia Hagenaars ◽  
...  

2021 ◽  
Vol 51 ◽  
pp. e207
Author(s):  
Aida Seyedsalehi ◽  
Richard Bethlehem ◽  
Varun Warrier ◽  
Benjamin Perry ◽  
Stephen Burgess ◽  
...  

2021 ◽  
Vol 51 ◽  
pp. e175-e176
Author(s):  
Francesco Casanova ◽  
Samuel Jones ◽  
Jessica O'Loughlin ◽  
Robin Beaumont ◽  
Andrew Wood ◽  
...  

2021 ◽  
Vol 51 ◽  
pp. e143-e144
Author(s):  
Yunqi Huang ◽  
Dongru Chen ◽  
Albert Levin ◽  
Brian Ahmedani ◽  
Cathrine Frank ◽  
...  

2021 ◽  
Vol 51 ◽  
pp. e113
Author(s):  
Vasileios Karageorgiou ◽  
Francesco Casanova ◽  
Jessica O'Loughlin ◽  
Jack Bowden ◽  
Jess Tyrrell

2021 ◽  
Vol 51 ◽  
pp. e64
Author(s):  
Christina Dardani ◽  
Jamie Robinson ◽  
Aws Sadik ◽  
Panagiota Pagoni ◽  
Jie Zheng ◽  
...  

Stroke ◽  
2021 ◽  
Author(s):  
Yap-Hang Chan ◽  
C. Mary Schooling ◽  
Jie Zhao ◽  
Shiu-Lun Au Yeung ◽  
Jo Jo Hai ◽  
...  

Background and Purpose: Experimental studies showed vitamin D (Vit-D) could promote vascular regeneration and repair. Prior randomized studies had focused mainly on primary prevention. Whether Vit-D protects against ischemic stroke and myocardial infarction recurrence among subjects with prior ischemic insults was unknown. Here, we dissected through Mendelian randomization any effect of Vit-D on the secondary prevention of recurrent ischemic stroke and myocardial infarction. Methods: Based on a genetic risk score for Vit-D constructed from a derivation cohort sample (n=5331, 45% Vit-D deficient, 89% genotyped) via high-throughput exome-chip screening of 12 prior genome-wide association study–identified genetic variants of Vit-D mechanistic pathways ( rs2060793 , rs4588 , and rs7041 ; F statistic, 73; P <0.001), we performed a focused analysis on prospective recurrence of myocardial infarction (MI) and ischemic stroke in an independent subsample with established ischemic disease (n=441, all with prior first ischemic event; follow-up duration, 41.6±14.3 years) under a 2-sample, individual-data, prospective Mendelian randomization approach. Results: In the ischemic disease subsample, 11.1% (n=49/441) had developed recurrent ischemic stroke or MI and 13.3% (n=58/441) had developed recurrent or de novo ischemic stroke/MI. Kaplan-Meier analyses showed that genetic risk score predicted improved event-free survival from recurrent ischemic stroke or MI (log-rank, 13.0; P =0.001). Cox regression revealed that genetic risk score independently predicted reduced risk of recurrent ischemic stroke or MI combined (hazards ratio, 0.62 [95% CI, 0.48–0.81]; P <0.001), after adjusted for potential confounders. Mendelian randomization supported that Vit-D is causally protective against the primary end points of recurrent ischemic stroke or MI (Wald estimate: odds ratio, 0.55 [95% CI, 0.35–0.81]) and any recurrent or de novo ischemic stroke/MI (odds ratio, 0.64 [95% CI, 0.42–0.91]) and recurrent MI alone (odds ratio, 0.52 [95% CI, 0.30–0.81]). Conclusions: Genetically predicted lowering in Vit-D level is causal for the recurrence of ischemic vascular events in persons with prior ischemic stroke or MI.


2021 ◽  
Author(s):  
Siqi Xu ◽  
Wing Kam Fung ◽  
Zhonghua Liu

Mendelian randomization (MR) utilizes genetic variants as instrumental variables (IVs) to estimate the causal effect of an exposure variable on an outcome of interest even in the presence of unmeasured confounders. However, many MR methods including the most popular inverse-variance weighted (IVW) estimator could be biased by the weak IVs that are weakly associated with the exposure. In this article, we develop a novel method called penalized inverse-variance weighted (pIVW) estimator, where we adjust the IVW estimator to account for the weak IVs by a proposed penalization method to prevent the denominator of the pIVW estimator from being close to zero. Moreover, we account for the horizontal pleiotropy|a widespread phenomenon in human genome that could bias the inference for the causal effect|by adjusting the variance estimation of the pIVW estimator. The proposed pIVW estimator can reduce to the debiased IVW (dIVW) estimator|another extension of the the IVW estimator|when the number of IVs and the IV strength increase. More generally, we prove that the pIVW estimator can achieve smaller bias and variance than the dIVW estimator under some regularity conditions. We also illustrate the improved performance of the proposed pIVW estimator over competing MR methods through a comprehensive simulation study. Further, we analyze the causal effects of the obesity-related traits and diseases on the Coronavirus disease 2019 (COVID-19). Notably, we find that hypertensive disease is associated with increased risk of hospitalized COVID-19, while peripheral vascular disease and higher body mass index are associated with increased risks of COVID-19 infection, hospitalized COVID-19 and critically ill COVID-19. The R package for the pIVW method is publicly available at https://github.com/siqixu/mr.pivw.


2021 ◽  
Vol 12 ◽  
Author(s):  
Hanxiao Chen ◽  
Yaoyao Zhang ◽  
Shangwei Li ◽  
Yuanzhi Tao ◽  
Rui Gao ◽  
...  

Polycystic ovary syndrome (PCOS) is one of the most common endocrine and metabolic diseases among women of reproductive age. Inflammation may be involved in the pathogenesis of PCOS, but its exact relationship with PCOS remains unclear. Herein, we investigate the causal association between systemic inflammatory regulators and PCOS risk through a two-sample Mendelian randomization (MR) approach based on the latest and largest genome-wide association study (GWAS) of 41 systemic inflammatory regulators in 8293 Finnish participants and a GWAS meta-analysis consisting of 10,074 PCOS cases and 103,164 controls of European ancestry. Our results suggest that higher levels of IL-17 and SDF1a, as well as lower levels of SCGFb and IL-4, are associated with an increased risk of PCOS (OR = 1.794, 95% CI = 1.150 – 2.801, P = 0.010; OR = 1.563, 95% CI = 1.055 – 2.315, P = 0.026; OR = 0.838, 95% CI = 0.712 – 0.986, P = 0.034; and OR = 0.637, 95% CI = 0.413 – 0.983, P = 0.042, respectively). In addition, genetically predicted PCOS is related to increased levels of IL-2 and VEGF (OR = 1.257, 95% CI = 1.022 – 1.546, P = 0.030 and OR = 1.112, 95% CI = 1.006 – 1.229, P = 0.038, respectively). Our results indicate the essential role of cytokines in the pathogenesis of PCOS. Further studies are warranted to assess the possibility of these biomarkers as targets for PCOS prevention and treatment.


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