Exploring the Relationship Between Caffeine Consumption, Caffeine Metabolism, and Sleep Behaviours: A Mendelian Randomisation Study.

Higher consumption of caffeinated beverages is associated with disturbed sleep patterns. Using genetic variants as proxies for caffeine consumption, caffeine metabolism, and sleep traits, we investigated whether this association reflects a direct effect of caffeine. Genetic variants associated with caffeine consumption (n = 407,072), caffeine metabolism (n = 9876), chronotype (n = 449,734), daytime napping (n = 452,633), daytime sleepiness (n = 452,071), getting up in morning (n = 385,949), insomnia (n = 453,379), and sleep duration (n = 446,118) identified in individuals from several studies, including the UK Biobank, were used to explore bi-directional causal relationships between caffeine and sleep using a series of univariable Mendelian Randomisation analyses.

Reassessing the validity of using weighted linear models to implement multi-generational GWAS-by-subtraction: a response to Evans et al.

Evans and colleagues for providing a critique on our article "Deriving GWAS summary estimates for paternal smoking in UK biobank: a GWAS by subtraction". They highlight important limitations in our approach, which we overlooked. They argue that our approach works neither in theory nor in practice- that there are both flaws in the method and in our execution of the method.

Lipid-lowering therapies for aortic stenosis: a drug-target Mendelian randomization study.

Introduction: Large observational and Mendelian randomization (MR) studies have demonstrated a strong association between both elevated LDL cholesterol (LDL-c) and triglycerides (TG) with risk of aortic stenosis (AS), although randomized trials showed no benefit of statins for AS. It consequently remains uncertain whether lipid-lowering therapies have a role to prevent or treat AS. We used a drug-target MR approach to investigate the genetically predicted effect of lipid-lowering therapies on risk of AS.

Silence is golden, but my measures still see-why cheaper-but-noisier outcome measures in large simple trials can be more cost-effective than gold standards.

Objective: To assess the cost-effectiveness of using cheaper-but-noisier outcome measures, such as a short questionnaire, for large simple clinical trials.

Background: To detect associations reliably, trials must avoid bias and random error. To reduce random error, we can increase the size of the trial and increase the accuracy of the outcome measurement process.

Independent Effects of Blood Pressure on Intraocular Pressure and Retinal Ganglion Cell Degeneration: A Mendelian Randomization Study.

Purpose: To investigate the causal effect of elevated blood pressure on primary open-angle glaucoma (POAG) and POAG endophenotypes.

Methods: Two-sample Mendelian randomization (MR) was performed to investigate the causal effect of elevated systolic blood pressure (SBP) (N = 757,601) and diastolic blood pressure (DBP) (N = 757,601) on intraocular pressure (IOP) (N = 139,555), macular retinal nerve fiber layer (mRNFL) thickness (N = 33,129), ganglion cell complex (GCC) thickness (N = 33,129), vertical cup-to-disc ratio (VCDR) (N = 111,724), and POAG liability (Ncases = 16,677, Ncontrols = 199,580). The primary analysis was conducted using the inverse-variance weighted approach.

MVMRmode: Introducing an R package for plurality valid estimators for multivariable Mendelian randomisation.

Background: Mendelian randomisation (MR) is the use of genetic variants as instrumental variables. Mode-based estimators (MBE) are one of the most popular types of estimators used in univariable-MR studies and is often used as a sensitivity analysis for pleiotropy. However, because there are no plurality valid regression estimators, modal estimators for multivariable-MR have been under-explored.

Multi-biobank summary data Mendelian randomisation does not support a causal effect of IL-6 signalling on risk of pulmonary arterial hypertension.

https://bit.ly/3T5h5uj

MRSamePopTest: introducing a simple falsification test for the two-sample mendelian randomisation 'same population' assumption.

Two-sample MR is an increasingly popular method for strengthening causal inference in epidemiological studies. For the effect estimates to be meaningful, variant-exposure and variant-outcome associations must come from comparable populations. A recent systematic review of two-sample MR studies found that, if assessed at all, MR studies evaluated this assumption by checking that the genetic association studies had similar demographics.

A drug target for erectile dysfunction to help improve fertility, sexual activity, and wellbeing: mendelian randomisation study.

Objective: To investigate the association of genetically proxied (using a surrogate biomarker) inhibition of phosphodiesterase 5 (PDE5), an established drug target for erectile dysfunction, with fertility, sexual behaviour, and subjective wellbeing.

Design: Two sample cis-mendelian randomisation study.

Setting: Summary data on genetic associations obtained from the International Consortium for Blood Pressure and UK Biobank.

Methods to increase response to postal and electronic questionnaires.

Background: Self-administered questionnaires are widely used to collect data in epidemiological research, but non-response reduces the effective sample size and can introduce bias. Finding ways to increase response to postal and electronic questionnaires would improve the quality of epidemiological research.

Objectives: To identify effective strategies to increase response to postal and electronic questionnaires.

MendelianRandomization v0.9.0: updates to an R package for performing Mendelian randomization analyses using summarized data.

The MendelianRandomization package is a software package written for the R software environment that implements methods for Mendelian randomization based on summarized data. In this manuscript, we describe functions that have been added or edited in the package since version 0.5.

Caffeine Intake, Plasma Caffeine Level, and Kidney Function: A Mendelian Randomization Study.

Caffeine is a psychoactive substance widely consumed worldwide, mainly via sources such as coffee and tea. The effects of caffeine on kidney function remain unclear. We leveraged the genetic variants in the and genes via the two-sample Mendelian randomization (MR) framework to estimate the association of genetically predicted plasma caffeine and caffeine intake on kidney traits.

Lipids, Blood Pressure, and Diabetes Mellitus on Risk of Cardiovascular Diseases in East Asians: A Mendelian Randomization Study.

Elevated blood pressure, dyslipidemia, and impaired glycemic control are well-established cardiovascular risk factors in Europeans, but there are comparatively few studies focused on East Asian populations. This study evaluated the potential causal relations between traditional cardiovascular risk factors and disease risk in East Asians through a 2-sample Mendelian randomization approach. We collected summary statistics for blood pressure parameters, lipid subsets, and type 2 diabetes mellitus liability from large genome-wide association study meta-analyses conducted in East Asians and Europeans.

Appraising the causal relationship between plasma caffeine levels and neuropsychiatric disorders through Mendelian randomization.

Background: Caffeine exposure modifies the turnover of monoamine neurotransmitters, which play a role in several neuropsychiatric disorders. We conducted a Mendelian randomization study to investigate whether higher plasma caffeine levels are causally associated with the risk of anorexia nervosa, bipolar disorder, major depressive disorder (MDD), and schizophrenia.

Methods: Summary-level data on the neuropsychiatric disorders were obtained from large-scale genome-wide association studies (GWASs) of European ancestry participants (n = 72,517 to 807,553) and meta-analyzed with the corresponding data from the FinnGen study (n = 356,077).

Deriving GWAS summary estimates for paternal smoking in UK biobank: a GWAS by subtraction.

Objective: To use genome-wide association study (GWAS) by subtraction, a method for deriving novel GWASs from existing summary statistics, to derive genome-wide summary statistics for paternal smoking.

Result: A GWAS by subtraction was implemented using a weighted linear model that defined the child-genotype paternal-phenotype association as the child-genotype child-phenotype association minus the child-genotype maternal-phenotype association. We first use the laws of inherence to derive the weighted linear model.

The UK BiLEVE and Mendelian randomisation: using multivariable instrumental variables to address "damned if you, damned if you don't" adjustment problems.

Objective: To explore the use of multivariable instrumental variables to resolve the "damned if you do, damned if you don't" adjustment problem created for Mendelian randomisation (MR) analysis using the smoking or lung function related phenotypes in the UK Biobank (UKB).

Result: "damned if you do, damned if you don't" adjustment problems occur when both adjusting and not-adjusting for a variable will induce bias in an analysis. One instance of this occurs because the genotyping chip of UKB participants differed based on lung function/smoking status.