Two‐Sample Multivariable Mendelian Randomization Analysis Using R

2021 ◽  
Vol 1 (12) ◽  
Author(s):  
Danielle Rasooly ◽  
Gina M. Peloso
2021 ◽  
Author(s):  
Abdolhalim Rajabi ◽  
Azadeh Shojaei ◽  
Leila Janani ◽  
Mojtaba Farjam ◽  
Hamid Reza Baradaran ◽  
...  

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 409
Author(s):  
Dhruba Tara Maharjan ◽  
Ali Alamdar Shah Syed ◽  
Guan Ning Lin ◽  
Weihai Ying

Testosterone’s role in female depression is not well understood, with studies reporting conflicting results. Here, we use meta-analytical and Mendelian randomization techniques to determine whether serum testosterone levels differ between depressed and healthy women and whether such a relationship is casual. Our meta-analysis shows a significant association between absolute serum testosterone levels and female depression, which remains true for the premenopausal group while achieving borderline significance in the postmenopausal group. The results from our Mendelian randomization analysis failed to show any causal relationship between testosterone and depression. Our results show that women with depression do indeed display significantly different serum levels of testosterone. However, the directions of the effect of this relationship are conflicting and may be due to menopausal status. Since our Mendelian randomization analysis was insignificant, the difference in testosterone levels between healthy and depressed women is most likely a manifestation of the disease itself. Further studies could be carried out to leverage this newfound insight into better diagnostic capabilities culminating in early intervention in female depression.


2014 ◽  
Vol 94 (2) ◽  
pp. 312 ◽  
Author(s):  
Michael V. Holmes ◽  
Leslie A. Lange ◽  
Tom Palmer ◽  
Matthew B. Lanktree ◽  
Kari E. North ◽  
...  

2021 ◽  
Author(s):  
Pedrum Mohammadi-Shemirani ◽  
Michael Chong ◽  
Nicolas Perrot ◽  
Marie Pigeyre ◽  
Gregory R. Steinberg ◽  
...  

Background: ATP-citrate lyase (ACLY) inhibition is a promising therapeutic target for dyslipidemia, atherosclerotic cardiovascular disease, non-alcoholic steatohepatitis, and metabolic syndrome. Genetic analysis of its role in chronic kidney disease (CKD) has not been performed. Methods: We constructed a genetic instrument by selecting variants associated with ACLY expression level in the expression quantitative trait loci genetics consortium (eQTLGen) that includes blood samples from 31,684 participants. In a two-sample Mendelian randomization analysis, we then evaluated the effect of genetically predicted ACLY expression on risk of CKD, estimated glomerular filtration rate (eGFR), and microalbuminuria using the CKD Genetics consortium (CKDGen), United Kingdom biobank, and the Finnish Genetics consortium (FinnGen) totaling 66,396 CKD cases and 958,517 controls. Results: ACLY is constitutively expressed in all cell types including in whole blood. The genetic instrument included 13 variants and explained 1.5% of variation in whole blood ACLY gene expression. A 34% reduction in genetically predicted ACLY expression was associated with a 0.04 mmol/L reduced low-density lipoprotein cholesterol (P = 3.4 x 10-4) and a 9% reduced risk of CKD (stage 3,4,5, dialysis or eGFR below 60 ml/min/1.73m2) (OR = 0.91, 95% C.I. 0.85-0.98, P = 0.008), but no association was observed with eGFR nor microalbuminuria. Conclusion: Mendelian Randomization analysis provides cautious optimism regarding the possibility of ACLY as a therapeutic target for CKD.


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